Scholars@Duke
Jorn Coers

Jorn Coers

Professor in Molecular Genetics and Microbiology
Molecular Genetics and Microbiology

Selected Publications

The Shigella flexneri effector IpaH1.4 facilitates RNF213 degradation and protects cytosolic bacteria against interferon-induced ubiquitylation.

Journal Article bioRxiv · September 5, 2024 A central signal that marshals host defense against many infections is the lymphocyte-derived cytokine interferon-gamma (IFNγ). The IFNγ receptor is expressed on most human cells and its activation leads to the expression of antimicrobial proteins that exe ... 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

Restriction and evasion: a review of IFNγ-mediated cell-autonomous defense pathways during genital Chlamydia infection.

Journal Article Pathog Dis · February 7, 2024 Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infection (STI) in the USA. As an STI, C. trachomatis infections can cause inflammatory damage to the female reproductive tract and downstream sequelae including infertility. ... Full text Link to item Cite

Overexpression of T3SS translocation signals in Salmonella causes delayed attenuation.

Journal Article Infect Immun · January 16, 2024 Engineering pathogens is a useful method for discovering new details of microbial pathogenesis and host defense. However, engineering can result in off-target effects. We previously engineered Salmonella enterica serovar Typhimurium to overexpress the secr ... Full text Link to item Cite

An aging-susceptible circadian rhythm controls cutaneous antiviral immunity.

Journal Article JCI Insight · October 23, 2023 Aged skin is prone to viral infections, but the mechanisms responsible for this immunosenescent immune risk are unclear. We observed that aged murine and human skin expressed reduced levels of antiviral proteins (AVPs) and circadian regulators, including B ... Full text Link to item Cite

Pyroptosis in defense against intracellular bacteria.

Journal Article Semin Immunol · September 2023 Pathogenic microbes invade the human body and trigger a host immune response to defend against the infection. In response, host-adapted pathogens employ numerous virulence strategies to overcome host defense mechanisms. As a result, the interaction between ... Full text Link to item Cite

A binary module for microbiota-mediated regulation of γδ17 cells, hallmarked by microbiota-driven expression of programmed cell death protein 1.

Journal Article Cell Rep · August 29, 2023 Little is known about how microbiota regulate innate-like γδ T cells or how these restrict their effector functions within mucosal barriers, where microbiota provide chronic stimulation. Here, we show that microbiota-mediated regulation of γδ17 cells is bi ... Full text Link to item Cite

An Aging-Susceptible Circadian Rhythm Controls Cutaneous Antiviral Immunity.

Conference bioRxiv · April 18, 2023 Aged skin is prone to viral infections, but the mechanisms responsible for this immunosenescent immune risk are unclear. We observed that aged murine and human skin expressed reduced antiviral proteins (AVPs) and circadian regulators including Bmal1 and Cl ... Full text Link to item Cite

LPS-aggregating proteins GBP1 and GBP2 are each sufficient to enhance caspase-4 activation both in cellulo and in vitro.

Journal Article Proc Natl Acad Sci U S A · April 11, 2023 The gamma-interferon (IFNγ)-inducible guanylate-binding proteins (GBPs) promote host defense against gram-negative cytosolic bacteria in part through the induction of an inflammatory cell death pathway called pyroptosis. To activate pyroptosis, GBPs facili ... Full text Link to item Cite

Shigella IpaH9.8 limits GBP1-dependent LPS release from intracytosolic bacteria to suppress caspase-4 activation.

Journal Article Proc Natl Acad Sci U S A · April 11, 2023 Pyroptosis is an inflammatory form of cell death induced upon recognition of invading microbes. During an infection, pyroptosis is enhanced in interferon-gamma-exposed cells via the actions of members of the guanylate-binding protein (GBP) family. GBPs pro ... Full text Link to item Cite

Differential Requirement for IRGM Proteins during Tuberculosis Infection in Mice.

Journal Article Infect Immun · February 16, 2023 Mycobacterium tuberculosis (Mtb) is a bacterium that exclusively resides in human hosts and remains a dominant cause of morbidity and mortality among infectious diseases worldwide. Host protection against Mtb infection is dependent on the function of immun ... Full text Link to item Cite

Mycobacterium tuberculosis Evasion of Guanylate Binding Protein-Mediated Host Defense in Mice Requires the ESX1 Secretion System.

Journal Article Int J Mol Sci · February 2, 2023 Cell-intrinsic immune mechanisms control intracellular pathogens that infect eukaryotes. The intracellular pathogen Mycobacterium tuberculosis (Mtb) evolved to withstand cell-autonomous immunity to cause persistent infections and disease. A potent inducer ... Full text Link to item Cite

An ancestral mycobacterial effector promotes dissemination of infection

Conference MOLECULAR BIOLOGY OF THE CELL · 2023 Cite

An ancestral mycobacterial effector promotes dissemination of infection

Conference MOLECULAR BIOLOGY OF THE CELL · 2023 Cite

The bacterial effector GarD shields Chlamydia trachomatis inclusions from RNF213-mediated ubiquitylation and destruction.

Journal Article Cell Host Microbe · December 14, 2022 Chlamydia trachomatis is the leading cause of sexually transmitted bacterial infections and a major threat to women's reproductive health in particular. This obligate intracellular pathogen resides and replicates within a cellular compartment termed an inc ... Full text Link to item Cite

An ancestral mycobacterial effector promotes dissemination of infection.

Journal Article Cell · November 23, 2022 The human pathogen Mycobacterium tuberculosis typically causes lung disease but can also disseminate to other tissues. We identified a M. tuberculosis (Mtb) outbreak presenting with unusually high rates of extrapulmonary dissemination and bone disease. We ... Full text Link to item Cite

Interferon-Inducible E3 Ligase RNF213 Facilitates Host-Protective Linear and K63-Linked Ubiquitylation of Toxoplasma gondii Parasitophorous Vacuoles.

Journal Article mBio · October 26, 2022 The obligate intracellular protozoan pathogen Toxoplasma gondii infects a wide range of vertebrate hosts and frequently causes zoonotic infections in humans. Whereas infected immunocompetent individuals typically remain asymptomatic, toxoplasmosis in immun ... Full text Link to item Cite

How did we get here? Insights into mechanisms of immunity-related GTPase targeting to intracellular pathogens.

Journal Article Curr Opin Microbiol · October 2022 The cytokine gamma-interferon activates cell-autonomous immunity against intracellular bacterial and protozoan pathogens by inducing a slew of antimicrobial proteins, some of which hinge upon immunity-related GTPases (IRGs) for their function. Three regula ... Full text Link to item Cite

IRF3 inhibits IFN-γ-mediated restriction of intracellular pathogens in macrophages independently of IFNAR.

Conference J Leukoc Biol · August 2022 Macrophages use an array of innate immune sensors to detect intracellular pathogens and to tailor effective antimicrobial responses. In addition, extrinsic activation with the cytokine IFN-γ is often required as well to tip the scales of the host-pathogen ... Full text Link to item Cite

Caspase-11 interaction with NLRP3 potentiates the noncanonical activation of the NLRP3 inflammasome.

Journal Article Nat Immunol · May 2022 Caspase-11 detection of intracellular lipopolysaccharide (LPS) from invasive Gram-negative bacteria mediates noncanonical activation of the NLRP3 inflammasome. While avirulent bacteria do not invade the cytosol, their presence in tissues necessitates clear ... 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

SNX10 and caspase-5 sort out endosomal LPS for a gut-wrenching Slug-fest.

Journal Article EMBO J · December 15, 2021 Endosomes are important cellular compartments for sorting internalized cargo and immune sensing. In this issue, Wang et al describe a novel signaling pathway induced by endocytosed bacterial outer membrane vesicles, where sorting nexin 10 and caspase-5 act ... 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

Human guanylate binding proteins: nanomachines orchestrating host defense.

Journal Article FEBS J · October 2021 Disease-causing microorganisms not only breach anatomical barriers and invade tissues but also frequently enter host cells, nutrient-enriched environments amenable to support parasitic microbial growth. Protection from many infectious diseases is therefore ... Full text Link to item Cite

The GBP1 microcapsule interferes with IcsA-dependent septin cage assembly around Shigella flexneri.

Journal Article Pathog Dis · April 24, 2021 Many cytosolic bacterial pathogens hijack the host actin polymerization machinery to form actin tails that promote direct cell-to-cell spread, enabling these pathogens to avoid extracellular immune defenses. However, these pathogens are still susceptible t ... Full text Link to item Cite

Immunopathogenesis of genital Chlamydia infection: insights from mouse models.

Journal Article Pathog Dis · March 31, 2021 Chlamydiae are pathogenic intracellular bacteria that cause a wide variety of diseases throughout the globe, affecting the eye, lung, coronary arteries and female genital tract. Rather than by direct cellular toxicity, Chlamydia infection generally causes ... 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

Guanylate Binding Proteins Restrict Leishmania donovani Growth in Nonphagocytic Cells Independent of Parasitophorous Vacuolar Targeting.

Journal Article mBio · July 28, 2020 Interferon (IFN)-inducible guanylate binding proteins (GBPs) play important roles in host defense against many intracellular pathogens that reside within pathogen-containing vacuoles (PVs). For instance, members of the GBP family translocate to PVs occupie ... Full text Link to item Cite

Direct binding of polymeric GBP1 to LPS disrupts bacterial cell envelope functions.

Journal Article EMBO J · July 1, 2020 In the outer membrane of gram-negative bacteria, O-antigen segments of lipopolysaccharide (LPS) form a chemomechanical barrier, whereas lipid A moieties anchor LPS molecules. Upon infection, human guanylate binding protein-1 (hGBP1) colocalizes with intrac ... Full text Link to item Cite

A Rapidly Evolving Polybasic Motif Modulates Bacterial Detection by Guanylate Binding Proteins.

Journal Article mBio · May 19, 2020 Cell-autonomous immunity relies on the rapid detection of invasive pathogens by host proteins. Guanylate binding proteins (GBPs) have emerged as key mediators of vertebrate immune defense through their ability to recognize a diverse array of intracellular ... 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 dist ... Full text Open Access Cite

IRG1 and Inducible Nitric Oxide Synthase Act Redundantly with Other Interferon-Gamma-Induced Factors To Restrict Intracellular Replication of Legionella pneumophila.

Journal Article mBio · November 12, 2019 Interferon gamma (IFN-γ) restricts the intracellular replication of many pathogens, but the mechanism by which IFN-γ confers cell-intrinsic pathogen resistance remains unclear. For example, intracellular replication of the bacterial pathogen Legionella pne ... Full text Link to item Cite

Genetic Screen in Chlamydia muridarum Reveals Role for an Interferon-Induced Host Cell Death Program in Antimicrobial Inclusion Rupture.

Journal Article mBio · April 9, 2019 Interferon-regulated immune defenses protect mammals from pathogenically diverse obligate intracellular bacterial pathogens of the genus Chlamydia Interferon gamma (IFN-γ) is especially important in controlling the virulence of Chlamydia species and thus i ... Full text Open Access Link to item Cite

Crohn's disease IRGM risk alleles are associated with altered gene expression in human tissues.

Journal Article Am J Physiol Gastrointest Liver Physiol · January 1, 2019 Crohn's disease (CD) is a chronic inflammatory gastrointestinal disorder. Genetic association studies have implicated dysregulated autophagy in CD. Among risk loci identified are a promoter single nucleotide polymorphism (SNP)( rs13361189 ) and two intrage ... Full text Link to item Cite

C57BL/6 and 129 inbred mouse strains differ in Gbp2 and Gbp2b expression in response to inflammatory stimuli in vivo.

Journal Article Wellcome Open Res · 2019 Background: Infections cause the production of inflammatory cytokines such as Interferon gamma (IFNγ). IFNγ in turn prompts the upregulation of a range of host defence proteins including members of the family of guanylate binding proteins (Gbps). In humans ... Full text Link to item Cite

A rapidly evolving polybasic motif modulates bacterial detection by guanylate binding proteins

Journal Article · 2019 Cell-autonomous immunity relies on the rapid detection of invasive pathogens by host proteins. Guanylate binding proteins (GBPs) have emerged as key mediators of vertebrate immune defense through their ability to recognize a diverse array of intracellular ... Full text Cite

IRG1 and iNOS act redundantly with other interferon gamma-induced factors to restrict intracellular replication ofLegionella pneumophila

Journal Article · 2019 Interferon gamma (IFNγ) restricts the intracellular replication of many pathogens, but how IFNγ confers cell-intrinsic pathogen resistance remains unclear. For example, intracellular replication of the bacterial pathogen Legionella pneumophila in macrophag ... Full text 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 Featured Publication 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

Constitutive Interferon Maintains GBP Expression Required for Release of Bacterial Components Upstream of Pyroptosis and Anti-DNA Responses.

Journal Article Cell Rep · July 3, 2018 Featured Publication Legionella pneumophila elicits caspase-11-driven macrophage pyroptosis through guanylate-binding proteins (GBPs) encoded on chromosome 3. It has been proposed that microbe-driven IFN upregulates GBPs to facilitate pathogen vacuole rupture and bacteriolysis ... Full text Link to item Cite

Detection of Cytosolic Shigella flexneri via a C-Terminal Triple-Arginine Motif of GBP1 Inhibits Actin-Based Motility.

Journal Article mBio · December 12, 2017 Featured Publication Dynamin-like guanylate binding proteins (GBPs) are gamma interferon (IFN-γ)-inducible host defense proteins that can associate with cytosol-invading bacterial pathogens. Mouse GBPs promote the lytic destruction of targeted bacteria in the host cell cytosol ... Full text Link to item Cite

Sweet host revenge: Galectins and GBPs join forces at broken membranes.

Journal Article Cell Microbiol · December 2017 Most bacterial pathogens enter and exit eukaryotic cells during their journey through the vertebrate host. In order to endure inside a eukaryotic cell, bacterial invaders commonly employ bacterial secretion systems to inject host cells with virulence facto ... Full text Link to item Cite

Inflammasome Activation by Bacterial Outer Membrane Vesicles Requires Guanylate Binding Proteins.

Journal Article mBio · October 3, 2017 The Gram-negative bacterial cell wall component lipopolysaccharide (LPS) is recognized by the noncanonical inflammasome protein caspase-11 in the cytosol of infected host cells and thereby prompts an inflammatory immune response linked to sepsis. Host guan ... Full text Open Access Link to item Cite

Guanylate Binding Proteins Regulate Inflammasome Activation in Response to Hyperinjected Yersinia Translocon Components.

Journal Article Infect Immun · October 2017 Gram-negative bacterial pathogens utilize virulence-associated secretion systems to inject, or translocate, effector proteins into host cells to manipulate cellular processes and promote bacterial replication. However, translocated bacterial products are s ... 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 Featured Publication 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 Featured Publication 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

Galectin-3 directs antimicrobial guanylate binding proteins to vacuoles furnished with bacterial secretion systems.

Journal Article Proc Natl Acad Sci U S A · February 28, 2017 Featured Publication Many invasive bacteria establish pathogen-containing vacuoles (PVs) as intracellular niches for microbial growth. Immunity to these infections is dependent on the ability of host cells to recognize PVs as targets for host defense. The delivery of several h ... Full text Link to item Cite

The Chlamydia trachomatis Inclusion Membrane Protein CpoS Counteracts STING-Mediated Cellular Surveillance and Suicide Programs.

Journal Article Cell Host Microbe · January 11, 2017 Featured Publication Evading cell death is critical for Chlamydia to maintain a replicative niche, but the underlying mechanisms are unknown. We screened a library of Chlamydia mutants for modulators of cell death. Inactivation of the inclusion membrane protein CpoS (Chlamydia ... Full text Link to item Cite

Detection of cytosolicShigella flexnerivia a C-terminal triple-arginine motif of GBP1 inhibits actin-based motility

Journal Article · 2017 Dynamin-like guanylate binding proteins (GBPs) are gamma interferon (IFNγ)-inducible host defense proteins that can associate with cytosol-invading bacterial pathogens. Mouse GBPs promote the lytic destruction of targeted bacteria in the host cell cytosol ... Full text Cite

Chlamydia trachomatis Is Resistant to Inclusion Ubiquitination and Associated Host Defense in Gamma Interferon-Primed Human Epithelial Cells.

Journal Article mBio · December 13, 2016 Featured Publication UNLABELLED: The cytokine gamma interferon (IFN-γ) induces cell-autonomous immunity to combat infections with intracellular pathogens, such as the bacterium Chlamydia trachomatis The present study demonstrates that IFN-γ-primed human cells ubiquitinate and ... Full text Link to item Cite

The Listeria monocytogenes PASTA Kinase PrkA and Its Substrate YvcK Are Required for Cell Wall Homeostasis, Metabolism, and Virulence.

Journal Article PLoS Pathog · November 2016 Obstacles to bacterial survival and replication in the cytosol of host cells, and the mechanisms used by bacterial pathogens to adapt to this niche are not well understood. Listeria monocytogenes is a well-studied Gram-positive foodborne pathogen that has ... Full text Link to item Cite

Sensing the enemy, containing the threat: cell-autonomous immunity to Chlamydia trachomatis.

Journal Article FEMS Microbiol Rev · November 1, 2016 Featured Publication The bacterium Chlamydia trachomatis is the etiological agent of the most common sexually transmitted infection in North America and Europe. Medical complications resulting from genital C. trachomatis infections arise predominantly in women where the initia ... Full text Link to item Cite

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

Journal Article J Mol Biol · August 28, 2016 Featured Publication 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

Human GBP1 does not localize to pathogen vacuoles but restricts Toxoplasma gondii.

Journal Article Cell Microbiol · August 2016 Guanylate binding proteins (GBPs) are a family of large interferon-inducible GTPases that are transcriptionally upregulated upon infection with intracellular pathogens. Murine GBPs (mGBPs) including mGBP1 and 2 localize to and disrupt pathogen-containing v ... Full text Link to item Cite

Sensing the enemy, containing the threat: cell-autonomous immunity to Chlamydia trachomatis.

Journal Article FEMS Microbiol Rev · July 29, 2016 The bacterium Chlamydia trachomatis is the etiological agent of the most common sexually transmitted infection in North America and Europe. Medical complications resulting from genital C. trachomatis infections arise predominantly in women where the initia ... Full text Link to item Cite

Erratum.

Journal Article Autophagy · 2016 Full text Link to item Cite

Guanylate binding proteins enable rapid activation of canonical and noncanonical inflammasomes in Chlamydia-infected macrophages.

Journal Article Infect Immun · December 2015 Featured Publication Interferon (IFN)-inducible guanylate binding proteins (GBPs) mediate cell-autonomous host resistance to bacterial pathogens and promote inflammasome activation. The prevailing model postulates that these two GBP-controlled activities are directly linked th ... Full text Link to item Cite

ID: 260

Conference Cytokine · November 2015 Full text Cite

Ubiquitin systems mark pathogen-containing vacuoles as targets for host defense by guanylate binding proteins.

Conference Proc Natl Acad Sci U S A · October 13, 2015 Many microbes create and maintain pathogen-containing vacuoles (PVs) as an intracellular niche permissive for microbial growth and survival. The destruction of PVs by IFNγ-inducible guanylate binding protein (GBP) and immunity-related GTPase (IRG) host pro ... Full text Link to item Cite

Canonical Inflammasomes Drive IFN-γ to Prime Caspase-11 in Defense against a Cytosol-Invasive Bacterium.

Journal Article Cell Host Microbe · September 9, 2015 The inflammatory caspases 1 and 11 are activated in response to different agonists and act independently to induce pyroptosis. In the context of IL-1β/IL-18 secretion, however, in vitro studies indicate that caspase-11 acts upstream of NLRP3 and caspase-1. ... Full text Link to item Cite

Ubiquitination of pathogen-containing vacuoles promotes host defense to Chlamydia trachomatis and Toxoplasma gondii.

Journal Article Commun Integr Biol · 2015 Many intracellular bacterial and protozoan pathogens reside within host cell vacuoles customized by the microbial invaders to fit their needs. Within such pathogen-containing vacuoles (PVs) microbes procure nutrients and simultaneously hide from cytosolic ... Full text Link to item Cite

Guanylate binding proteins promote caspase-11-dependent pyroptosis in response to cytoplasmic LPS.

Journal Article Proc Natl Acad Sci U S A · April 22, 2014 Featured Publication IFN receptor signaling induces cell-autonomous immunity to infections with intracellular bacterial pathogens. Here, we demonstrate that IFN-inducible guanylate binding protein (Gbp) proteins stimulate caspase-11-dependent, cell-autonomous immunity in respo ... Full text Link to item Cite

The E2-like conjugation enzyme Atg3 promotes binding of IRG and Gbp proteins to Chlamydia- and Toxoplasma-containing vacuoles and host resistance.

Journal Article PLoS One · 2014 Cell-autonomous immunity to the bacterial pathogen Chlamydia trachomatis and the protozoan pathogen Toxoplasma gondii is controlled by two families of Interferon (IFN)-inducible GTPases: Immunity Related GTPases (IRGs) and Guanylate binding proteins (Gbps) ... Full text Link to item Cite

Search for microRNAs expressed by intracellular bacterial pathogens in infected mammalian cells.

Journal Article PLoS One · 2014 MicroRNAs are expressed by all multicellular organisms and play a critical role as post-transcriptional regulators of gene expression. Moreover, different microRNA species are known to influence the progression of a range of different diseases, including c ... Full text Open Access 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 Featured Publication 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

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

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

Coordinated loading of IRG resistance GTPases on to the Toxoplasma gondii parasitophorous vacuole.

Journal Article Cell Microbiol · July 2010 The immunity-related GTPases (IRGs) constitute an interferon-induced intracellular resistance mechanism in mice against Toxoplasma gondii. IRG proteins accumulate on the parasitophorous vacuole membrane (PVM), leading to its disruption and to death of the ... Full text Link to item 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

Pronounced thrombocytosis in transgenic mice expressing reduced levels of Mpl in platelets and terminally differentiated megakaryocytes.

Journal Article Blood · February 19, 2009 We generated mice expressing a full-length Mpl transgene under the control of a 2-kb Mpl promoter in an Mpl(-/-) background, effectively obtaining mice that express full-length Mpl in the absence of other Mpl isoforms. These mice developed thrombocytosis w ... 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 Featured Publication 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

Restriction of Legionella pneumophila growth in macrophages requires the concerted action of cytokine and Naip5/Ipaf signalling pathways.

Journal Article Cell Microbiol · October 2007 Featured Publication Macrophages from the C57BL/6 (B6) mouse strain restrict intracellular growth of Legionella pneumophila, whereas A/J macrophages are highly permissive. The mechanism by which B6 macrophages restrict Legionella growth remains poorly understood, but is known ... 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

Genetic analysis of susceptibility to Chlamydia trachomatis in mouse.

Journal Article Genes Immun · March 2006 Featured Publication Chlamydia trachomatis is a bacterial pathogen that is a major cause of blindness and infertility in diverse populations across the world. In an effort to model genetic complexities that are observed in human populations and to identify novel genes involved ... Full text Link to item Cite

A truncated isoform of c-Mpl with an essential C-terminal peptide targets the full-length receptor for degradation.

Journal Article J Biol Chem · August 27, 2004 Thrombopoietin and its cognate receptor c-Mpl are the primary regulators of megakaryopoiesis and platelet production. They also play an important role in the maintenance of hematopoietic stem cells. Here, we have analyzed the function of a truncated Mpl re ... Full text Link to item Cite

Comparison of molecular markers in a cohort of patients with chronic myeloproliferative disorders.

Journal Article Blood · September 1, 2003 Decreased expression of c-MPL protein in platelets, increased expression of polycythemia rubra vera 1 (PRV-1) and nuclear factor I-B (NFIB) mRNA in granulocytes, and loss of heterozygosity on chromosome 9p (9pLOH) were described as molecular markers for my ... Full text Link to item Cite

Identification of Icm protein complexes that play distinct roles in the biogenesis of an organelle permissive for Legionella pneumophila intracellular growth.

Journal Article Mol Microbiol · November 2000 Legionella pneumophila is a bacterial pathogen that can enter the human lung and grow inside alveolar macrophages. To grow within phagocytic host cells, the bacteria must create a specialized organelle that restricts fusion with lysosomes. Biogenesis of th ... Full text Link to item Cite