Scholars@Duke
Gregory Alan Taylor

Gregory Alan Taylor

Professor in Medicine
Medicine, Geriatrics and Palliative Care
gregory.taylor@duke.edu
Duke Box 3003, Durham, NC 27710
182 GRECC VA Med Ctr, 508 Fulton St, Durham, NC 27705

Scholarly Works - Journal articles

Irgm1 Restrains CD8+ T Cell Cytokine Production and Apoptosis via Cell-Extrinsic Regulation of Type I Interferon Signaling.

Journal article Eur J Immunol · April 2026 Immunity-related GTPases (IRGs) are a family of proteins that maintain cellular homeostasis by promoting autophagy and mitophagy. Mutations in human IRGM and genetic deletion of mouse Irgm1 have been linked to increased severity of inflammatory bowel disea ... Full text Link to item Cite

Differential roles for Irgm1 in myeloid cells for immune resistance to pathogenic bacteria.

Journal article J Leukoc Biol · December 1, 2025 IRGM proteins are associated with increased susceptibility to Crohn's disease, mycobacterial infections, sepsis, and other inflammatory diseases, but the cells in which they function in vivo have not been delineated. To address this, mice with conditional ... Full text Link to item Cite

Accelerated Epigenetic Aging and Prospective Morbidity and Mortality Among U.S. Veterans.

Journal article J Gerontol A Biol Sci Med Sci · June 10, 2025 BACKGROUND: Epigenetic aging measures have promise as surrogate health outcomes in randomized control trials and observational cohort studies. The value of these measures, however, will reflect the extent to which they are associated with prospective healt ... Full text Link to item Cite

Accelerated biological aging and midlife frailty among U.S. military veterans.

Journal article J Gerontol A Biol Sci Med Sci · January 2, 2025 Injuries characterizing recent military service, such as traumatic brain injury and posttraumatic stress disorder, are linked to accelerated biological aging. If recent veterans have accelerated aging, they might also show early onset of aging-related phen ... Full text Link to item Cite

Type I interferon signaling and peroxisomal dysfunction contribute to enhanced inflammatory cytokine production in IRGM1-deficient macrophages.

Journal article J Biol Chem · November 2024 The human IRGM gene has been linked to inflammatory diseases including sepsis and Crohn's disease. Decreased expression of human IRGM, or the mouse orthologues Irgm1 and Irgm2, leads to increased production of a number of inflammatory chemokines and cytoki ... Full text Link to item Cite

Accelerated epigenetic aging and prospective morbidity and mortality among U.S. veterans.

Journal article medRxiv · October 23, 2024 Epigenetic measures of aging derived from DNA methylation are promising biomarkers associated with prospective morbidity and mortality, but require validation in real-world medical settings. Using data from 2,216 post-9/11 veterans, we examined whether acc ... Full text Link to item Cite

Irgm proteins attenuate inflammatory disease in mouse models of genital Chlamydia infection.

Journal article mBio · April 10, 2024 UNLABELLED: Chlamydiae are obligate intracellular bacterial pathogens that may cause genital pathology via induction of destructive host immune responses. Human-adapted Chlamydia trachomatis causes inflammatory disease in human hosts but is easily cleared ... Full text Link to item Cite

Posttraumatic stress disorder, trauma, and accelerated biological aging among post-9/11 veterans.

Journal article Transl Psychiatry · January 6, 2024 People who experience trauma and develop posttraumatic stress disorder (PTSD) are at increased risk for poor health. One mechanism that could explain this risk is accelerated biological aging, which is associated with the accumulation of chronic diseases, ... Full text Open Access Link to item Cite

Which Types of Stress Are Associated With Accelerated Biological Aging? Comparing Perceived Stress, Stressful Life Events, Childhood Adversity, and Posttraumatic Stress Disorder.

Journal article Psychosom Med · June 1, 2023 OBJECTIVE: Stress and stressful events are associated with poorer health; however, there are multiple ways to conceptualize and measure stress and stress responses. One physiological mechanism through which stress could result in poorer health is accelerat ... Full text Link to item Cite

IFN-λ is protective against lethal oral Toxoplasma gondii infection.

Journal article bioRxiv · February 24, 2023 Interferons are essential for innate and adaptive immune responses against a wide variety of pathogens. Interferon lambda (IFN-λ) protects mucosal barriers during pathogen exposure. The intestinal epithelium is the first contact site for Toxoplasma gondii ... Full text Link to item Cite

ROP39 is an Irgb10-specific parasite effector that modulates acute Toxoplasma gondii virulence.

Journal article PLoS Pathog · January 2023 Toxoplasma gondii (T. gondii) is a zoonotic apicomplexan parasite that is an important cause of clinical disability in humans. On a global scale, one third of the human population is infected with T. gondii. Mice and other small rodents are believed to be ... Full text Link to item Cite

Meteorin-like is an injectable peptide that can enhance regeneration in aged muscle through immune-driven fibro/adipogenic progenitor signaling.

Journal article Nat Commun · December 9, 2022 Pathologies associated with sarcopenia include decline in muscular strength, lean mass and regenerative capacity. Despite the substantial impact on quality of life, no pharmacological therapeutics are available to counteract the age-associated decline in f ... Full text Link to item Cite

Enterocyte-innate lymphoid cell crosstalk drives early IFN-γ-mediated control of Cryptosporidium.

Journal article Mucosal Immunol · February 2022 The intestinal parasite, Cryptosporidium, is a major contributor to global child mortality and causes opportunistic infection in immune deficient individuals. Innate resistance to Cryptosporidium, which specifically invades enterocytes, is dependent on the ... Full text Link to item Cite

Irgm1 regulates metabolism and function in T cell subsets.

Journal article Sci Rep · January 17, 2022 Immunity Related GTPases (IRG) are a family of proteins produced during infection that regulate membrane remodeling events in cells, particularly autophagy and mitophagy. The human IRGM gene has been strongly associated with Crohn's disease and other infla ... Full text Link to item Cite

Interactions of Autophagy and the Immune System in Health and Diseases.

Journal article Autophagy Rep · 2022 Autophagy is a highly conserved process that utilizes lysosomes to selectively degrade a variety of intracellular cargo, thus providing quality control over cellular components and maintaining cellular regulatory functions. Autophagy is triggered by multip ... Full text Link to item Cite

Murine Irgm Paralogs Regulate Nonredundant Functions To Execute Host Defense to Toxoplasma gondii.

Journal article Infect Immun · October 15, 2021 Gamma interferon (IFN-γ)-induced immunity-related GTPases (IRGs) confer cell-autonomous immunity to the intracellular protozoan pathogen Toxoplasma gondii. Effector IRGs are loaded onto the Toxoplasma-containing parasitophorous vacuole (PV), where they rec ... Full text Link to item Cite

IRGM1 links mitochondrial quality control to autoimmunity.

Journal article Nat Immunol · March 2021 Mitochondrial abnormalities have been noted in lupus, but the causes and consequences remain obscure. Autophagy-related genes ATG5, ATG7 and IRGM have been previously implicated in autoimmune disease. We reasoned that failure to clear defective mitochondri ... Full text Link to item Cite

Dynamin-related Irgm proteins modulate LPS-induced caspase-11 activation and septic shock.

Journal article EMBO Rep · November 5, 2020 Inflammation associated with gram-negative bacterial infections is often instigated by the bacterial cell wall component lipopolysaccharide (LPS). LPS-induced inflammation and resulting life-threatening sepsis are mediated by the two distinct LPS receptors ... Full text Link to item Cite

Glucagon-like peptide 2 for intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans.

Journal article Blood · September 17, 2020 Acute graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). Although currently used GVHD treatment regimens target the donor immune system, we explored here an approach that aims ... Full text Link to item Cite

Naïve CD8 T cell IFNγ responses to a vacuolar antigen are regulated by an inflammasome-independent NLRP3 pathway and Toxoplasma gondii ROP5.

Journal article PLoS pathogens · August 2020 Host resistance to Toxoplasma gondii relies on CD8 T cell IFNγ responses, which if modulated by the host or parasite could influence chronic infection and parasite transmission between hosts. Since host-parasite interactions that govern this response are n ... Full text Cite

Irgm1-deficiency leads to myeloid dysfunction in colon lamina propria and susceptibility to the intestinal pathogen Citrobacter rodentium.

Journal article PLoS Pathog · May 2020 IRGM and its mouse orthologue Irgm1 are dynamin-like proteins that regulate vesicular remodeling, intracellular microbial killing, and pathogen immunity. IRGM dysfunction is linked to inflammatory bowel disease (IBD), and while it is thought that defective ... Full text Link to item Cite

Dynamin-related Irgm proteins modulate LPS-induced caspase-4 activation and septic shock

Journal article · 2020 ABSTRACT Inflammation associated with gram-negative bacterial infections is often instigated by the bacterial cell wall component lipopolysaccharide (LPS). LPS-induced inflammation and resulting life-threatening sepsis are mediated by the two dis ... Full text Open Access Cite

Toxoplasma gondii Parasitophorous Vacuole Membrane-Associated Dense Granule Proteins Orchestrate Chronic Infection and GRA12 Underpins Resistance to Host Gamma Interferon.

Journal article mBio · July 2, 2019 Toxoplasma gondii evades host immunity to establish a chronic infection. Here, we assessed the role of parasitophorous vacuole (PV) membrane (PVM)- and intravacuolar network (IVN) membrane-localized dense granule (GRA) proteins in the development of acute ... Full text Link to item Cite

The Crohn's Disease Risk Factor IRGM Limits NLRP3 Inflammasome Activation by Impeding Its Assembly and by Mediating Its Selective Autophagy.

Journal article Mol Cell · February 7, 2019 Several large-scale genome-wide association studies genetically linked IRGM to Crohn's disease and other inflammatory disorders in which the IRGM appears to have a protective function. However, the mechanism by which IRGM accomplishes this anti-inflammator ... Full text Link to item Cite

Rhoptry and Dense Granule Secreted Effectors Regulate CD8+ T Cell Recognition of Toxoplasma gondii Infected Host Cells.

Journal article Front Immunol · 2019 Toxoplasma gondii secretes rhoptry (ROP) and dense granule (GRA) effector proteins to evade host immune clearance mediated by interferon gamma (IFN-γ), immunity-related GTPase (IRG) effectors, and CD8+ T cells. Here, we investigated the role of parasite-se ... Full text Link to item Cite

Partners in anti-crime: how interferon-inducible GTPases and autophagy proteins team up in cell-intrinsic host defense.

Journal article Curr Opin Immunol · October 2018 Once pathogens have breached the mechanical barriers to infection, survived extracellular immunity and successfully invaded host cells, cell-intrinsic immunity becomes the last line of defense to protect the mammalian host against viruses, bacteria, fungi ... Full text Link to item Cite

Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice.

Journal article Dis Model Mech · February 7, 2018 Crohn's disease (CD) represents a chronic inflammatory disorder of the intestinal tract. Several susceptibility genes have been linked to CD, though their precise role in the pathogenesis of this disorder remains unclear. Immunity-related GTPase M (IRGM) i ... Full text Link to item Cite

Irgm1 coordinately regulates autoimmunity and host defense at select mucosal surfaces.

Journal article JCI Insight · August 17, 2017 The pathogenesis of primary Sjogren's syndrome (SS), an autoimmune disease that targets the mucosa of exocrine tissues, is poorly understood. Although several mouse models have been developed that display features of SS, most of these are within the larger ... Full text Link to item Cite

Viral Replication Complexes Are Targeted by LC3-Guided Interferon-Inducible GTPases.

Journal article Cell Host Microbe · July 12, 2017 All viruses with positive-sense RNA genomes replicate on membranous structures in the cytoplasm called replication complexes (RCs). RCs provide an advantageous microenvironment for viral replication, but it is unknown how the host immune system counteracts ... Full text Link to item Cite

Metabolic Alterations Contribute to Enhanced Inflammatory Cytokine Production in Irgm1-deficient Macrophages.

Journal article J Biol Chem · March 17, 2017 The immunity-related GTPases (IRGs) are a family of proteins that are induced by interferon (IFN)-γ and play pivotal roles in immune and inflammatory responses. IRGs ostensibly function as dynamin-like proteins that bind to intracellular membranes and prom ... Full text Link to item Cite

Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism.

Journal article Nat Commun · November 14, 2016 Cross-talk between the gut microbiota and the host immune system regulates host metabolism, and its dysregulation can cause metabolic disease. Here, we show that the gut microbe Akkermansia muciniphila can mediate negative effects of IFNγ on glucose tolera ... Full text Link to item Cite

mTOR is critical for intestinal T-cell homeostasis and resistance to Citrobacter rodentium.

Journal article Sci Rep · October 12, 2016 T-cells play an important role in promoting mucosal immunity against pathogens, but the mechanistic basis for their homeostasis in the intestine is still poorly understood. We report here that T-cell-specific deletion of mTOR results in dramatically decrea ... Full text Link to item Cite

Interferon-Inducible GTPases in Host Resistance, Inflammation and Disease.

Journal article J Mol Biol · August 28, 2016 Cell-autonomous immunity is essential for host organisms to defend themselves against invasive microbes. In vertebrates, both the adaptive and the innate branches of the immune system operate cell-autonomous defenses as key effector mechanisms that are ind ... Full text Link to item Cite

Erratum.

Journal article Autophagy · 2016 Full text Link to item Cite

IFN-γ-induced macrophage antileishmanial mechanisms in mice: A role for immunity-related GTPases, Irgm1 and Irgm3, in Leishmania donovani infection in the liver.

Journal article Exp Parasitol · October 2015 In C57BL/6 mice, Leishmania donovani infection in the liver provoked IFN-γ-induced expression of the immunity-related GTPases (IRG), Irgm1 and Irgm3. To gauge the antileishmanial effects of these macrophage factors in the liver, intracellular infection was ... Full text Link to item Cite

IRGM3 contributes to immunopathology and is required for differentiation of antigen-specific effector CD8+ T cells in experimental cerebral malaria.

Journal article Infect Immun · April 2015 Gamma interferon (IFN-γ) drives antiparasite responses and immunopathology during infection with Plasmodium species. Immunity-related GTPases (IRGs) are a class of IFN-γ-dependent proteins that are essential for cell autonomous immunity to numerous intrace ... Full text Link to item Cite

Palmitoylation of the immunity related GTPase, Irgm1: impact on membrane localization and ability to promote mitochondrial fission.

Journal article PLoS One · 2014 The Immunity-Related GTPases (IRG) are a family of large GTPases that mediate innate immune responses. Irgm1 is particularly critical for immunity to bacteria and protozoa, and for inflammatory homeostasis in the intestine. Although precise functions for I ... Full text Link to item Cite

Irgm1-deficient mice exhibit Paneth cell abnormalities and increased susceptibility to acute intestinal inflammation.

Journal article Am J Physiol Gastrointest Liver Physiol · October 15, 2013 Crohn's disease (CD) is a chronic, immune-mediated, inflammatory disorder of the intestine that has been linked to numerous susceptibility genes, including the immunity-related GTPase (IRG) M (IRGM). IRGs comprise a family of proteins known to confer resis ... Full text Link to item Cite

Blood pressure homeostasis is maintained by a P311-TGF-β axis.

Journal article J Clin Invest · October 2013 P311 is an 8-kDa intracellular protein that is highly conserved across species and is expressed in the nervous system as well as in vascular and visceral smooth muscle cells. P311-null (P311-/-) mice display learning and memory defects, but alterations in ... Full text Link to item Cite

Irgm1 (LRG-47), a regulator of cell-autonomous immunity, does not localize to mycobacterial or listerial phagosomes in IFN-γ-induced mouse cells.

Journal article J Immunol · August 15, 2013 The IFN-inducible protein Irgm1 (LRG-47) belongs to the family of immunity-related GTPases that function in cell-autonomous resistance against intracellular pathogens in mice. Irgm1 deficiency is associated with a severe immunodeficiency syndrome. The prot ... Full text Link to item Cite

IRG and GBP host resistance factors target aberrant, "non-self" vacuoles characterized by the missing of "self" IRGM proteins.

Journal article PLoS Pathog · 2013 Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs and GBPs stably associate with pathogen-containing vacuoles (PVs) and elicit immune ... Full text Link to item Cite

Enhanced fitness: a randomized controlled trial of the effects of home-based physical activity counseling on glycemic control in older adults with prediabetes mellitus.

Journal article J Am Geriatr Soc · September 2012 OBJECTIVES: To determine whether a home-based multicomponent physical activity counseling (PAC) intervention is effective in reducing glycemic measures in older outpatients with prediabetes mellitus. DESIGN: Controlled clinical trial. SETTING: Primary care ... Full text Open Access Link to item Cite

Guidelines for the use and interpretation of assays for monitoring autophagy.

Journal article Autophagy · April 2012 In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have ... Full text Link to item Cite

Discovery of a novel Toxoplasma gondii conoid-associated protein important for parasite resistance to reactive nitrogen intermediates.

Journal article J Immunol · April 1, 2012 Toxoplasma gondii modifies its host cell to suppress its ability to become activated in response to IFN-γ and TNF-α and to develop intracellular antimicrobial effectors, including NO. Mechanisms used by T. gondii to modulate activation of its infected host ... Full text Link to item Cite

The polymorphic pseudokinase ROP5 controls virulence in Toxoplasma gondii by regulating the active kinase ROP18.

Journal article PLoS Pathog · 2012 Secretory polymorphic serine/threonine kinases control pathogenesis of Toxoplasma gondii in the mouse. Genetic studies show that the pseudokinase ROP5 is essential for acute virulence, but do not reveal its mechanism of action. Here we demonstrate that ROP ... Full text Link to item Cite

The immunity-related GTPase Irgm3 relieves endoplasmic reticulum stress response during coxsackievirus B3 infection via a PI3K/Akt dependent pathway.

Journal article Cell Microbiol · January 2012 The IRG protein Irgm3 preserves cell survival during coxsackievirus B3 (CVB3) infection. However, the molecular mechanisms are not clear. Here, we examined the effect of Irgm3 expression on ER stress triggered by pharmacological agents or CVB3 infection. I ... Full text Link to item Cite

Lessons learned when innovations go awry: a baseline description of a behavioral trial-the Enhancing Fitness in Older Overweight Veterans with Impaired Fasting Glucose study.

Journal article Transl Behav Med · November 2011 Individuals diagnosed with impaired glucose tolerance (i.e., prediabetes) are at increased risk for developing diabetes. We proposed a clinical trial with a novel adaptive randomization designed to examine the impact of a home-based physical activity (PA) ... Full text Open Access Link to item Cite

Dissection of a type I interferon pathway in controlling bacterial intracellular infection in mice.

Journal article Cell Microbiol · November 2011 Defence mechanisms against intracellular bacterial pathogens are incompletely understood. Our study characterizes a type I IFN-dependent cell-autonomous defence pathway directed against Legionella pneumophila, an intracellular model organism and frequent c ... Full text Link to item Cite

Immunity-related GTPase M (IRGM) proteins influence the localization of guanylate-binding protein 2 (GBP2) by modulating macroautophagy.

Journal article J Biol Chem · September 2, 2011 The immunity-related GTPases (IRGs) are a family of proteins induced by interferon-γ that play a crucial role in innate resistance to intracellular pathogens. The M subfamily of IRG proteins (IRGM) plays a profound role in this context, in part because of ... Full text Link to item Cite

Irgm1 protects hematopoietic stem cells by negative regulation of IFN signaling.

Journal article Blood · August 11, 2011 The IFN-inducible immunity-related p47 GTPase Irgm1 has been linked to Crohn disease as well as susceptibility to tuberculosis. Previously we demonstrated that HSC quiescence and function are aberrant in mice lacking Irgm1. To investigate the molecular bas ... Full text Link to item Cite

Compensatory T cell responses in IRG-deficient mice prevent sustained Chlamydia trachomatis infections.

Journal article PLoS Pathog · June 2011 The obligate intracellular pathogen Chlamydia trachomatis is the most common cause of bacterial sexually transmitted diseases in the United States. In women C. trachomatis can establish persistent genital infections that lead to pelvic inflammatory disease ... Full text Link to item Cite

Plasma acylcarnitines are associated with physical performance in elderly men.

Journal article J Gerontol A Biol Sci Med Sci · May 2011 BACKGROUND: Metabolic profiling might provide insight into the biologic underpinnings of disability in older adults. METHODS: A targeted mass spectrometry-based platform was used to identify and quantify 45 plasma acylcarnitines in 77 older men with a mean ... Full text Link to item Cite

Nitric oxide-mediated intracellular growth restriction of pathogenic Rhodococcus equi can be prevented by iron.

Journal article Infect Immun · May 2011 Rhodococcus equi is an intracellular pathogen which causes pneumonia in young horses and in immunocompromised humans. R. equi arrests phagosome maturation in macrophages at a prephagolysosome stage and grows inside a privileged compartment. Here, we show t ... Full text Link to item Cite

Phosphorylation of immunity-related GTPases by a Toxoplasma gondii-secreted kinase promotes macrophage survival and virulence.

Journal article Cell Host Microbe · December 16, 2010 Macrophages are specialized to detect and destroy intracellular microbes and yet a number of pathogens have evolved to exploit this hostile niche. Here we demonstrate that the obligate intracellular parasite Toxoplasma gondii disarms macrophage innate clea ... Full text Link to item Cite

cPLA2 regulates the expression of type I interferons and intracellular immunity to Chlamydia trachomatis.

Journal article J Biol Chem · July 9, 2010 Infection with the obligate bacterial intracellular pathogen Chlamydia trachomatis leads to the sustained activation of the small GTPase RAS and many of its downstream signaling components. In particular, the mitogen-activated protein kinase ERK and the ca ... Full text Link to item Cite

Genetic deficiency of Irgm1 (LRG-47) suppresses induction of experimental autoimmune encephalomyelitis by promoting apoptosis of activated CD4+ T cells.

Journal article FASEB J · May 2010 The immunity-related GTPase Irgm1, also called LRG-47, is known to regulate host resistance to intracellular pathogens through multiple mechanisms that include controlling the survival of T lymphocytes. Here, we address whether Irgm1 also plays a role in t ... Full text Link to item Cite

Regulation of macrophage motility by Irgm1.

Journal article J Leukoc Biol · February 2010 IRG are a family of IFN-regulated proteins that are critical for resistance to infection. Mouse IRG proteins are divided into GMS and GKS subfamilies, based on a sequence within the G1 GTP-binding motif. The GMS proteins have a particularly profound impact ... Full text Link to item Cite

Localisation and mislocalisation of the interferon-inducible immunity-related GTPase, Irgm1 (LRG-47) in mouse cells.

Journal article PLoS One · January 13, 2010 Irgm1 (LRG-47) is an interferon-inducible Golgi membrane associated GTPase of the mouse whose disruption causes susceptibility to many different intracellular pathogens. Irgm1 has been variously interpreted as a regulator of homologous effector GTPases of ... Full text Open Access Link to item Cite

Localisation and mislocalisation of the interferon-inducible immunity-related GTPase, Irgm1 (LRG-47) in mouse cells

Journal article PLoS ONE · 2010 Irgm1 (LRG-47) is an interferon-inducible Golgi membrane associated GTPase of the mouse whose disruption causes susceptibility to many different intracellular pathogens. Irgm1 has been variously interpreted as a regulator of homologous effector GTPases of ... Full text Cite

Balance of Irgm protein activities determines IFN-gamma-induced host defense.

Journal article J Leukoc Biol · May 2009 The immunity-related GTPases (IRG), also known as p47 GTPases, are a family of proteins that are tightly regulated by IFNs at the transcriptional level and serve as key mediators of IFN-regulated resistance to intracellular bacteria and protozoa. Among the ... Full text Link to item Cite

Behavioral characterization of P311 knockout mice.

Journal article Genes Brain Behav · October 2008 P311 is an 8-kDa protein that is expressed in many brain regions, particularly the hippocampus, cerebellum and olfactory lobes, and is under stringent regulation by developmental, mitogenic and other physiological stimuli. P311 is thought to be involved in ... Full text Link to item Cite

TLR adaptor MyD88 is essential for pathogen control during oral toxoplasma gondii infection but not adaptive immunity induced by a vaccine strain of the parasite.

Journal article J Immunol · September 1, 2008 TLR adaptor MyD88 activation is important in host resistance to Toxoplasma gondii during i.p. infection, but the function of this signaling pathway during oral infection, in which mucosal immunity assumes a predominant role, has not been examined. In this ... Full text Link to item Cite

Focal adhesion kinase mediates the interferon-gamma-inducible GTPase-induced phosphatidylinositol 3-kinase/Akt survival pathway and further initiates a positive feedback loop of NF-kappaB activation.

Journal article Cell Microbiol · September 2008 Interferon-gamma-inducible GTPase (IGTP) expression is upregulated in coxsackievirus B3 (CVB3)-infected murine heart and inhibits CVB3-induced apoptosis through activation of the PI3 kinase/Akt pathway. However, the mechanism of this pathway activation is ... Full text Link to item Cite

Involvement of P311 in the affective, but not in the sensory component of pain.

Journal article Mol Pain · June 12, 2008 Pain is comprised of the sensory and affective components. Compared to the well-investigated mechanisms of the sensory pain, much less is known about the mechanisms underlying the affective pain. In recent years, accumulating evidence suggests that the ant ... Full text Link to item Cite

Chlamydia muridarum evades growth restriction by the IFN-gamma-inducible host resistance factor Irgb10.

Journal article J Immunol · May 1, 2008 Chlamydiae are obligate intracellular bacterial pathogens that exhibit a broad range of host tropism. Differences in host tropism between Chlamydia species have been linked to host variations in IFN-gamma-mediated immune responses. In mouse cells, IFN-gamm ... Full text Link to item Cite

The p47 GTPase Lrg-47 (Irgm1) links host defense and hematopoietic stem cell proliferation.

Journal article Cell Stem Cell · January 10, 2008 Hematopoietic stem cells (HSCs) are self-renewing bone marrow cells that give rise to all blood lineages and retain a remarkable capacity to proliferate in response to insult. Although some controls on HSC activation are known, little is understood about h ... Full text Link to item Cite

Impaired macrophage function underscores susceptibility to Salmonella in mice lacking Irgm1 (LRG-47).

Journal article J Immunol · November 15, 2007 Featured Publication IRG proteins, or immunity-related GTPases (also known as p47 GTPases), are a group of IFN-regulated proteins that are highly expressed in response to infection. The proteins localize to intracellular membranes including vacuoles that contain pathogens in i ... Full text Link to item Cite

The IFN-inducible GTPase LRG47 (Irgm1) negatively regulates TLR4-triggered proinflammatory cytokine production and prevents endotoxemia.

Journal article J Immunol · October 15, 2007 Featured Publication LRG47/Irgm1, a 47-kDa IFN-inducible GTPase, plays a major role in regulating host resistance as well as the hemopoietic response to intracellular pathogens. LRG47 expression in macrophages has been shown previously to be stimulated in vitro by bacterial LP ... Full text Link to item Cite

IRG proteins: key mediators of interferon-regulated host resistance to intracellular pathogens.

Journal article Cell Microbiol · May 2007 Featured Publication Immunity-related GTPases (IRG) (also known as p47 GTPases) are a family of proteins found in vertebrates, which play critical roles in mediating innate resistance to intracellular pathogens. The proteins are expressed at high levels following infection wit ... Full text Link to item Cite

Macrophage activation downregulates the degradative capacity of the phagosome.

Journal article Traffic · March 2007 Featured Publication The phagosome is key to most macrophage functions. It is the site of degradation of particulate material, of bacterial killing and the generation of peptides for antigen presentation. Despite its role at the fulcrum of the innate and acquired immune system ... Full text Link to item Cite

Control of IFN-gamma-mediated host resistance to intracellular pathogens by immunity-related GTPases (p47 GTPases).

Journal article Microbes Infect · 2007 Featured Publication IRG proteins (also known as p47 GTPases) are key mediators of interferon-gamma-induced resistance to pathogens. Absence of certain IRG proteins leads to profound susceptibility to protozoa and bacteria in mice. Underlying their roles in host resistance, IR ... Full text Link to item Cite

The p47 GTPases Igtp and Irgb10 map to the Chlamydia trachomatis susceptibility locus Ctrq-3 and mediate cellular resistance in mice.

Journal article Proc Natl Acad Sci U S A · September 19, 2006 Featured Publication Infections caused by the bacteria Chlamydia trachomatis contribute to diverse pathologies in a variety of human populations. We previously used a systemic model of C. trachomatis infection in mice to map three quantitative trait loci that influence in vivo ... Full text Link to item Cite

Human IRGM induces autophagy to eliminate intracellular mycobacteria.

Journal article Science · September 8, 2006 Featured Publication Immunity-related p47 guanosine triphosphatases (IRG) play a role in defense against intracellular pathogens. We found that the murine Irgm1 (LRG-47) guanosine triphosphatase induced autophagy and generated large autolysosomal organelles as a mechanism for ... Full text Link to item Cite

Vacuolar and plasma membrane stripping and autophagic elimination of Toxoplasma gondii in primed effector macrophages.

Journal article J Exp Med · September 4, 2006 Featured Publication Apicomplexan protozoan pathogens avoid destruction and establish a replicative niche within host cells by forming a nonfusogenic parasitophorous vacuole (PV). Here we present evidence for lysosome-mediated degradation of Toxoplasma gondii after invasion of ... Full text Link to item Cite

Vacuolar and plasma membrane stripping and autophagic elimination of Toxoplasma gondii in primed effector macrophages

Journal article Journal of Experimental Medicine · September 4, 2006 Apicomplexan protozoan pathogens avoid destruction and establish a replicative niche within host cells by forming a nonfusogenic parasitophorous vacuole (PV). Here we present evidence for lysosome-mediated degradation of Toxoplasma gondii after invasion of ... Full text Cite

Mice deficient in LRG-47 display enhanced susceptibility to Trypanosoma cruzi infection associated with defective hemopoiesis and intracellular control of parasite growth.

Journal article J Immunol · December 15, 2005 IFN-gamma is known to be required for host control of intracellular Trypanosoma cruzi infection in mice, although the basis of its protective function is poorly understood. LRG-47 is an IFN-inducible p47GTPase that has been shown to regulate host resistanc ... Full text Link to item Cite

p47 GTPases regulate Toxoplasma gondii survival in activated macrophages.

Journal article Infect Immun · June 2005 Featured Publication The cytokine gamma interferon (IFN-gamma) is critical for resistance to Toxoplasma gondii. IFN-gamma strongly activates macrophages and nonphagocytic host cells to limit intracellular growth of T. gondii; however, the cellular factors that are required for ... Full text Link to item Cite

Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages.

Journal article Cell · December 17, 2004 Featured Publication Mycobacterium tuberculosis is an intracellular pathogen persisting within phagosomes through interference with phagolysosome biogenesis. Here we show that stimulation of autophagic pathways in macrophages causes mycobacterial phagosomes to mature into phag ... Full text Link to item Cite

Elevated expression of a subset of interferon inducible genes in primary bone marrow cells expressing p185 Bcr-Abl versus p210 Bcr-Abl by DNA microarray analysis.

Journal article Leuk Res · March 2004 Featured Publication p185 Bcr-Abl has a more aggressive biological/clinical leukemia phenotype than p210 Bcr-Abl. In this study, we examined differential gene expression using microarrays to determine if upregulation or downregulation of specific genes may explain the distinct ... Full text Link to item Cite

STAT1 is essential for antimicrobial effector function but dispensable for gamma interferon production during Toxoplasma gondii infection.

Journal article Infect Immun · March 2004 Featured Publication The opportunistic protozoan Toxoplasma gondii is a prototypic Th1-inducing pathogen inducing strong gamma interferon (IFN-gamma) cytokine responses that are required to survive infection. Intracellular signaling intermediate STAT1 mediates many effects of ... Full text Link to item Cite

p47 GTPases: regulators of immunity to intracellular pathogens.

Journal article Nat Rev Immunol · February 2004 Featured Publication Activation of the innate immune system by interferon-gamma (IFN-gamma is crucial for host resistance to infection. IFN-gamma induces the expression of a wide range of mediators that undermine the ability of pathogens to survive in host cells, including a n ... Full text Link to item Cite

Mice deficient in LRG-47 display increased susceptibility to mycobacterial infection associated with the induction of lymphopenia.

Journal article J Immunol · January 15, 2004 Featured Publication Although IFN-gamma is essential for host control of mycobacterial infection, the mechanisms by which the cytokine restricts pathogen growth are only partially understood. LRG-47 is an IFN-inducible GTP-binding protein previously shown to be required for IF ... Full text Link to item Cite

Absence of interferon-gamma-inducible gene IGTP does not significantly alter the development of chagasic cardiomyopathy in mice infected with Trypanosoma cruzi (Brazil strain).

Journal article J Parasitol · December 2003 Featured Publication Interferon-gamma (IFN-gamma) contributes to host resistance during acute infection with Trypanosoma cruzi, the causative agent of Chagas' disease. Inducibly expressed guanosine triphosphatase (IGTP), a 48-kDa guanosine triphosphatase (GTPase), is a member ... Full text Link to item Cite

Immune control of tuberculosis by IFN-gamma-inducible LRG-47.

Journal article Science · October 24, 2003 Featured Publication Interferon-gamma (IFN-gamma) provides an essential component of immunity to tuberculosis by activating infected host macrophages to directly inhibit the replication of Mycobacterium tuberculosis (Mtb). IFN-gamma-inducible nitric oxide synthase 2 (NOS2) is ... Full text Link to item Cite

The function of gamma interferon-inducible GTP-binding protein IGTP in host resistance to Toxoplasma gondii is Stat1 dependent and requires expression in both hematopoietic and nonhematopoietic cellular compartments.

Journal article Infect Immun · December 2002 Featured Publication IGTP is a member of the 47-kDa family of gamma interferon (IFN-gamma)-induced GTPases. We have previously shown that IGTP is critical for host resistance to Toxoplasma gondii infection. In the present study, we demonstrate that T. gondii-induced IGTP expre ... Full text Link to item Cite

P311 induces a TGF-beta1-independent, nonfibrogenic myofibroblast phenotype.

Journal article J Clin Invest · November 2002 Featured Publication P311, also called PTZ17, was identified by suppressive subtraction hybridization as potentially involved in smooth muscle (SM) myogenesis. P311 is an 8-kDa protein with several PEST-like motifs found in neurons and muscle. P311 transfection into two fibrob ... Full text Link to item Cite

Gamma interferon-induced inhibition of Toxoplasma gondii in astrocytes is mediated by IGTP.

Journal article Infect Immun · September 2001 Featured Publication Toxoplasma gondii is an important pathogen in the central nervous system, causing a severe and often fatal encephalitis in patients with AIDS. Gamma interferon (IFN-gamma) is the main cytokine preventing reactivation of Toxoplasma encephalitis in the brain ... Full text Link to item Cite

Inactivation of LRG-47 and IRG-47 reveals a family of interferon gamma-inducible genes with essential, pathogen-specific roles in resistance to infection.

Journal article J Exp Med · July 16, 2001 Featured Publication The cytokine interferon (IFN)-gamma regulates immune clearance of parasitic, bacterial, and viral infections; however, the underlying mechanisms are poorly understood. Recently, a family of IFN-gamma-induced genes has been identified that encode 48-kD GTP- ... Full text Link to item Cite

Regulation of P311 expression by Met-hepatocyte growth factor/scatter factor and the ubiquitin/proteasome system.

Journal article J Biol Chem · February 11, 2000 Featured Publication P311 is a mouse cDNA originally identified for its high expression in late-stage embryonic brain and adult cerebellum, hippocampus, and olfactory bulb. The protein product of P311, however, had not been identified previously, and its function remains unkno ... Full text Link to item Cite

Pathogen-specific loss of host resistance in mice lacking the IFN-gamma-inducible gene IGTP.

Journal article Proc Natl Acad Sci U S A · January 18, 2000 Featured Publication Interferon-gamma (IFN-gamma) is critical for defense against pathogens, but the molecules that mediate its antimicrobial responses are largely unknown. IGTP is the prototype for a family of IFN-gamma-regulated genes that encode 48-kDa GTP-binding proteins ... Full text Link to item Cite

The von Hippel-Lindau tumor suppressor gene inhibits hepatocyte growth factor/scatter factor-induced invasion and branching morphogenesis in renal carcinoma cells.

Journal article Mol Cell Biol · September 1999 Featured Publication Loss of function in the von Hippel-Lindau (VHL) tumor suppressor gene occurs in familial and most sporadic renal cell carcinomas (RCCs). VHL has been linked to the regulation of cell cycle cessation (G(0)) and to control of expression of various mRNAs such ... Full text Link to item Cite

Evidence for a role of Met-HGF/SF during Ras-mediated tumorigenesis/metastasis.

Journal article Oncogene · October 22, 1998 Featured Publication Aberrations in Met-hepatocyte growth factor/scatter factor (HGF/SF) signaling have been implicated in the acquisition of tumorigenic and metastatic phenotypes. Here we show that murine NIH3T3 and C127 cells transformed by the Ras oncogene overexpress the M ... Full text Link to item Cite

Decreased fibronectin expression in Met/HGF-mediated tumorigenesis.

Journal article Oncogene · September 3, 1998 Featured Publication The tyrosine kinase receptor Met and its ligand, hepatocyte growth factor (HGF)/scatter factor are involved in the etiology and progression of a number of human cancers. Coexpression of Met and HGF in mesenchymal cells increases the tumorigenic and metasta ... Full text Link to item Cite

Met and hepatocyte growth factor/scatter factor expression in human gliomas.

Journal article Cancer Res · December 1, 1997 Using double immunofluorescence staining and quantitative confocal laser scan microscopy, we show that the intensity of hepatocyte growth factor/scatter factor (HGF/SF) and Met staining in human primary brain tumors increases with the grade of malignancy a ... Link to item Cite

The inducibly expressed GTPase localizes to the endoplasmic reticulum, independently of GTP binding.

Journal article J Biol Chem · April 18, 1997 Featured Publication The inducibly expressed GTPase (IGTP) is representative of a newly identified group of interferon gamma-inducible GTPases, whose functions are currently unknown. We have begun to address the cellular function of IGTP by examining its subcellular distributi ... Full text Link to item Cite

Degradation of the Met tyrosine kinase receptor by the ubiquitin-proteasome pathway.

Journal article Mol Cell Biol · February 1997 Featured Publication The Met tyrosine kinase receptor is a widely expressed molecule which mediates pleiotropic cellular responses following activation by its ligand, hepatocyte growth factor/scatter factor (HGF/SF). In this communication we demonstrate that significant Met de ... Full text Link to item Cite

Cloning and characterization of two yeast genes encoding members of the CCCH class of zinc finger proteins: zinc finger-mediated impairment of cell growth.

Journal article Gene · October 3, 1996 Featured Publication Members of the CCCH zinc finger (Zf) protein family have in common two or more repeats of a novel Zf motif consisting of Cys and His residues in the form Cx8Cx5Cx3H [where x is a variable amino acid (aa)]. We used a degenerate polymerase chain reaction (PC ... Full text Link to item Cite

Identification of a novel GTPase, the inducibly expressed GTPase, that accumulates in response to interferon gamma.

Journal article J Biol Chem · August 23, 1996 Featured Publication Interferon gamma is a pleiotropic cytokine that regulates many immune functions. We have identified a novel protein, inducibly expressed GTPase (IGTP), whose expression was regulated by interferon gamma in macrophages. In mouse RAW 264.7 macrophages, IGTP ... Full text Link to item Cite

A pathogenetic role for TNF alpha in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency.

Journal article Immunity · May 1996 Featured Publication Tristetraprolin (TTP) is a widely expressed potential transcription factor that contains two unusual CCCH zinc fingers and is encoded by the immediate-early response gene, Zfp-36. Mice made deficient in TTP by gene targeting appeared normal at birth, but s ... Full text Link to item Cite

Mitogens stimulate the rapid nuclear to cytosolic translocation of tristetraprolin, a potential zinc-finger transcription factor.

Journal article Mol Endocrinol · February 1996 Featured Publication Tristetraprolin (TTP) is the prototype of a group of potential transcription factors that contain two or more unusual CCCH zinc fingers. TTP is encoded by the immediate-early response gene Zfp-36, which is rapidly induced in fibroblasts in response to insu ... Full text Link to item Cite

Promoter analysis of Zfp-36, the mitogen-inducible gene encoding the zinc finger protein tristetraprolin.

Journal article J Biol Chem · October 20, 1995 Featured Publication The gene encoding the putative zinc finger protein tristetraprolin (TTP), Zfp-36, is rapidly induced by a variety of mitogens and growth factors. We show here that 77 base pairs 5' of the transcription start site are sufficient for full serum inducibility ... Full text Link to item Cite

Phosphorylation of tristetraprolin, a potential zinc finger transcription factor, by mitogen stimulation in intact cells and by mitogen-activated protein kinase in vitro.

Journal article J Biol Chem · June 2, 1995 Featured Publication Tristetraprolin (TTP) is a potential transcription factor that contains three PPPPG repeats and two putative CCCH zinc fingers. TTP is encoded by the early response gene Zfp-36, which is highly expressed in response to growth factors and in several hematop ... Full text Link to item Cite

Zinc inhibits turnover of labile mRNAs in intact cells.

Journal article J Cell Physiol · March 1995 Featured Publication For immediate early genes such as the c-fos proto-oncogene, mRNA breakdown is very rapid and is largely responsible for the transient nature of mRNA accumulation after transcription is stimulated. We found that in several types of cultured cells and in mic ... Full text Link to item Cite