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Edward A. Miao

Chancellor's Distinguished Professor of Immunology
Integrative Immunobiology
Box 103054, Durham, NC 27710
3 Genome Ct; DUMC Box 103054, Durham, NC 27710

Selected Publications


Caspase-1 activates gasdermin A in non-mammals.

Journal Article Elife · March 18, 2024 Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of ... Full text Link to item Cite

Caspase-1 activates gasdermin A in non-mammals

Journal Article eLife · March 18, 2024 Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker reg ... Full text Cite

Validation of the Intermolecular Disulfide Bond in Caspase-2.

Journal Article Biology (Basel) · January 17, 2024 Caspases are a family of proteins involved in cell death. Although several caspase members have been well characterized, caspase-2 remains enigmatic. Caspase-2 has been implicated in several phenotypes, but there has been no consensus in the field about it ... 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

Neutrophils only die twice.

Journal Article Sci Adv · December 22, 2023 After apoptotic cell death begins neutrophils initiate NETosis, a second cell death program. ... Full text Link to item Cite

Apoptotic signaling clears engineered Salmonella in an organ-specific manner.

Journal Article Elife · December 6, 2023 Pyroptosis and apoptosis are two forms of regulated cell death that can defend against intracellular infection. When a cell fails to complete pyroptosis, backup pathways will initiate apoptosis. Here, we investigated the utility of apoptosis compared to py ... Full text Link to item Cite

Apoptotic signaling clears engineered Salmonella in an organ-specific manner

Journal Article eLife · December 6, 2023 Pyroptosis and apoptosis are two forms of regulated cell death that can defend against intracellular infection. When a cell fails to complete pyroptosis, backup pathways will initiate apoptosis. Here, we investigated the utility of apoptosis compar ... Full text Cite

Production of a p65fl/fl/LysMCre mouse model with dysfunctional NF-κB signaling in bone marrow-derived macrophages.

Journal Article Innate Immun · November 2023 Here, we describe the production and characterization of a novel p65fl/fl/LysMCre mouse model, which lacks canonical nuclear factor-kappaB member RelA/p65 (indicated as p65 hereafter) in bone marrow-derived macrophages. Cultured bone marrow-derived macroph ... Full text Link to item Cite

An innate granuloma eradicates an environmental pathogen using Gsdmd and Nos2.

Journal Article Nat Commun · October 21, 2023 Granulomas often form around pathogens that cause chronic infections. Here, we discover an innate granuloma model in mice with an environmental bacterium called Chromobacterium violaceum. Granuloma formation not only successfully walls off, but also clears ... Full text Link to item Cite

Bucket lists must be completed during cell death.

Journal Article Trends Cell Biol · September 2023 Regulated cell death occurs in many forms, including apoptosis, pyroptosis, necroptosis, and NETosis. Most obviously, the purpose of these pathways is to kill the cell. However, many cells need to complete a set of effector programs before they die, which ... 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

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

Journal Article Cell Death Differ · May 2023 Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process ... Full text Link to item Cite

Neutrophil inflammasomes sense the subcellular delivery route of translocated bacterial effectors and toxins.

Journal Article Cell Rep · November 22, 2022 In neutrophils, caspase-11 cleaves gasdermin D (GSDMD), causing pyroptosis to clear cytosol-invasive bacteria. In contrast, caspase-1 also cleaves GSDMD but seems to not cause pyroptosis. Here, we show that this pyroptosis-resistant caspase-1 activation is ... Full text Link to item Cite

Role of Caspases and Gasdermin A during HSV-1 Infection in Mice.

Journal Article Viruses · September 13, 2022 Herpes simplex virus type 1 (HSV-1) infection can manifest locally as mucocutaneous lesions or keratitis and can also spread to the central nervous system to cause encephalitis. HSV-1 establishes a lifelong latent infection and neither cure nor vaccine is ... Full text Link to item Cite

Caspase-7 activates ASM to repair gasdermin and perforin pores.

Journal Article Nature · June 2022 Among the caspases that cause regulated cell death, a unique function for caspase-7 has remained elusive. Caspase-3 performs apoptosis, whereas caspase-7 is typically considered an inefficient back-up. Caspase-1 activates gasdermin D pores to lyse the cell ... Full text Link to item Cite

Innate Sensors Trigger Regulated Cell Death to Combat Intracellular Infection.

Journal Article Annu Rev Immunol · April 26, 2022 Intracellular pathogens pose a significant threat to animals. In defense, innate immune sensors attempt to detect these pathogens using pattern recognition receptors that either directly detect microbial molecules or indirectly detect their pathogenic acti ... Full text Link to item Cite

The AIM2 inflammasome is activated in astrocytes during the late phase of EAE.

Journal Article JCI Insight · April 22, 2022 Inflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity against pathogens and inflammatory respon ... Full text Link to item Cite

Caspase-1 activates gasdermin A in non-mammals.

Journal Article Elife · March 18, 2024 Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of ... Full text Link to item Cite

Caspase-1 activates gasdermin A in non-mammals

Journal Article eLife · March 18, 2024 Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker reg ... Full text Cite

Validation of the Intermolecular Disulfide Bond in Caspase-2.

Journal Article Biology (Basel) · January 17, 2024 Caspases are a family of proteins involved in cell death. Although several caspase members have been well characterized, caspase-2 remains enigmatic. Caspase-2 has been implicated in several phenotypes, but there has been no consensus in the field about it ... 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

Neutrophils only die twice.

Journal Article Sci Adv · December 22, 2023 After apoptotic cell death begins neutrophils initiate NETosis, a second cell death program. ... Full text Link to item Cite

Apoptotic signaling clears engineered Salmonella in an organ-specific manner.

Journal Article Elife · December 6, 2023 Pyroptosis and apoptosis are two forms of regulated cell death that can defend against intracellular infection. When a cell fails to complete pyroptosis, backup pathways will initiate apoptosis. Here, we investigated the utility of apoptosis compared to py ... Full text Link to item Cite

Apoptotic signaling clears engineered Salmonella in an organ-specific manner

Journal Article eLife · December 6, 2023 Pyroptosis and apoptosis are two forms of regulated cell death that can defend against intracellular infection. When a cell fails to complete pyroptosis, backup pathways will initiate apoptosis. Here, we investigated the utility of apoptosis compar ... Full text Cite

Production of a p65fl/fl/LysMCre mouse model with dysfunctional NF-κB signaling in bone marrow-derived macrophages.

Journal Article Innate Immun · November 2023 Here, we describe the production and characterization of a novel p65fl/fl/LysMCre mouse model, which lacks canonical nuclear factor-kappaB member RelA/p65 (indicated as p65 hereafter) in bone marrow-derived macrophages. Cultured bone marrow-derived macroph ... Full text Link to item Cite

An innate granuloma eradicates an environmental pathogen using Gsdmd and Nos2.

Journal Article Nat Commun · October 21, 2023 Granulomas often form around pathogens that cause chronic infections. Here, we discover an innate granuloma model in mice with an environmental bacterium called Chromobacterium violaceum. Granuloma formation not only successfully walls off, but also clears ... Full text Link to item Cite

Bucket lists must be completed during cell death.

Journal Article Trends Cell Biol · September 2023 Regulated cell death occurs in many forms, including apoptosis, pyroptosis, necroptosis, and NETosis. Most obviously, the purpose of these pathways is to kill the cell. However, many cells need to complete a set of effector programs before they die, which ... 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

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

Journal Article Cell Death Differ · May 2023 Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process ... Full text Link to item Cite

Neutrophil inflammasomes sense the subcellular delivery route of translocated bacterial effectors and toxins.

Journal Article Cell Rep · November 22, 2022 In neutrophils, caspase-11 cleaves gasdermin D (GSDMD), causing pyroptosis to clear cytosol-invasive bacteria. In contrast, caspase-1 also cleaves GSDMD but seems to not cause pyroptosis. Here, we show that this pyroptosis-resistant caspase-1 activation is ... Full text Link to item Cite

Role of Caspases and Gasdermin A during HSV-1 Infection in Mice.

Journal Article Viruses · September 13, 2022 Herpes simplex virus type 1 (HSV-1) infection can manifest locally as mucocutaneous lesions or keratitis and can also spread to the central nervous system to cause encephalitis. HSV-1 establishes a lifelong latent infection and neither cure nor vaccine is ... Full text Link to item Cite

Caspase-7 activates ASM to repair gasdermin and perforin pores.

Journal Article Nature · June 2022 Among the caspases that cause regulated cell death, a unique function for caspase-7 has remained elusive. Caspase-3 performs apoptosis, whereas caspase-7 is typically considered an inefficient back-up. Caspase-1 activates gasdermin D pores to lyse the cell ... Full text Link to item Cite

Innate Sensors Trigger Regulated Cell Death to Combat Intracellular Infection.

Journal Article Annu Rev Immunol · April 26, 2022 Intracellular pathogens pose a significant threat to animals. In defense, innate immune sensors attempt to detect these pathogens using pattern recognition receptors that either directly detect microbial molecules or indirectly detect their pathogenic acti ... Full text Link to item Cite

The AIM2 inflammasome is activated in astrocytes during the late phase of EAE.

Journal Article JCI Insight · April 22, 2022 Inflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity against pathogens and inflammatory respon ... Full text Link to item Cite

Shigella handcuffs caspases.

Journal Article Nat Microbiol · January 2022 Full text Link to item Cite

Autophagy May Allow a Cell to Forbear Pyroptosis When Confronted With Cytosol-Invasive Bacteria.

Journal Article Front Immunol · 2022 Inflammatory caspases detect cytosol-invasive Gram-negative bacteria by monitoring for the presence of LPS in the cytosol. This should provide defense against the cytosol-invasive Burkholderia and Shigella species by lysing the infected cell via pyroptosis ... Full text Link to item Cite

Post-Translational Modifications of Proteins in Cytosolic Nucleic Acid Sensing Signaling Pathways.

Journal Article Front Immunol · 2022 The innate immune response is the first-line host defense against pathogens. Cytosolic nucleic acids, including both DNA and RNA, represent a special type of danger signal to initiate an innate immune response. Activation of cytosolic nucleic acid sensors ... Full text Link to item Cite

AIM2 inflammasome activation in astrocytes occurs during the late phase of EAE

Journal Article · October 5, 2021 ABSTRACTInflammasomes are a class of innate immune signaling platforms that activate in response to an array of cellular damage and pathogens. Inflammasomes promote inflammation under many circumstances to enhance immunity ... Full text Cite

Evaluating cytokine production by flow cytometry using brefeldin A in mice.

Journal Article STAR Protoc · March 19, 2021 Characterizing cytokine production in situ is important for properly understanding immunologic responses. Cytokine reporter mice are limited by the need to cross markers into various knockout backgrounds and by availability of reporters of interest. To ove ... Full text Link to item Cite

Non-Cell-Autonomous Activity of the Hemidesmosomal Protein BP180/Collagen XVII in Granulopoiesis in Humanized NC16A Mice.

Journal Article J Immunol · November 15, 2020 BP180 (also termed type XVII collagen) is a hemidesmosomal protein and plays a critical role in cell-cell matrix adhesion in the skin; however, its other biological functions are largely unclear. In this study, we generated a BP180 functional-deficient mou ... Full text Link to item Cite

LPS-binding IgG arrests actively motile Salmonella Typhimurium in gastrointestinal mucus.

Journal Article Mucosal Immunol · September 2020 The gastrointestinal (GI) mucosa is coated with a continuously secreted mucus layer that serves as the first line of defense against invading enteric bacteria. We have previously shown that antigen-specific immunoglobulin G (IgG) can immobilize viruses in ... Full text Link to item Cite

Neutrophil Caspase-11 Is Essential to Defend against a Cytosol-Invasive Bacterium.

Journal Article Cell Rep · July 28, 2020 Either caspase-1 or caspase-11 can cleave gasdermin D to cause pyroptosis, eliminating intracellular replication niches. We previously showed that macrophages detect Burkholderia thailandensis via NLRC4, triggering the release of interleukin (IL)-18 and dr ... Full text Link to item Cite

Author Correction: Reactive oxygen species induce antibiotic tolerance during systemic Staphylococcus aureus infection.

Journal Article Nat Microbiol · March 2020 An amendment to this paper has been published and can be accessed via a link at the top of the paper. ... Full text Link to item Cite

Programmed Cell Death in the Evolutionary Race against Bacterial Virulence Factors.

Journal Article Cold Spring Harb Perspect Biol · February 3, 2020 Innate immune sensors can recognize when host cells are irrevocably compromised by pathogens, and in response can trigger programmed cell death (pyroptosis, apoptosis, and necroptosis). Innate sensors can directly bind microbial ligands; for example, NAIP/ ... Full text Link to item Cite

Reactive oxygen species induce antibiotic tolerance during systemic Staphylococcus aureus infection.

Journal Article Nat Microbiol · February 2020 Staphylococcus aureus is a major human pathogen that causes an array of infections ranging from minor skin infections to more serious infections, including osteomyelitis, endocarditis, necrotizing pneumonia and sepsis1. These more serious infections usuall ... Full text Link to item Cite

NLRP1 - One NLR to guard them all.

Journal Article EMBO J · July 1, 2019 Microbial pathogens can be detected by inflammasomes that induce inflammation and programmed cell death. Inflammasomes are sensors that survey cells for signs of compromise. One of these sensors, NLRP1, detects anthrax lethal toxin; however, the mechanism ... Full text Link to item Cite

Environmental Factors Modify the Severity of Acute DSS Colitis in Caspase-11-Deficient Mice.

Journal Article Inflamm Bowel Dis · October 12, 2018 BACKGROUND: Human and mouse studies implicate the inflammasome in the pathogenesis of inflammatory bowel diseases, though the effects in mice are variable. The noncanonical inflammasome activator caspase-11 (Casp11) reportedly attenuates acute dextran sodi ... Full text Link to item Cite

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Journal Article Cell Death Differ · March 2018 Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel ... Full text Open Access Link to item Cite

Lipopolysaccharide Potentiates Insulin-Driven Hypoglycemic Shock.

Journal Article J Immunol · November 15, 2017 Critically ill patients typically present with hyperglycemia. Treatment with conventional insulin therapy (targeting 144-180 mg/dl) improves patient survival; however, intensive insulin therapy (IIT) targeting normal blood glucose levels (81-108 mg/dl) inc ... Full text Link to item Cite

Caspase-11-mediated endothelial pyroptosis underlies endotoxemia-induced lung injury.

Journal Article J Clin Invest · November 1, 2017 Acute lung injury is a leading cause of death in bacterial sepsis due to the wholesale destruction of the lung endothelial barrier, which results in protein-rich lung edema, influx of proinflammatory leukocytes, and intractable hypoxemia. Pyroptosis is a f ... Full text Link to item Cite

Gasdermins: Effectors of Pyroptosis.

Journal Article Trends Cell Biol · September 2017 Pyroptosis is a form of lytic programmed cell death initiated by inflammasomes, which detect cytosolic contamination or perturbation. This drives activation of caspase-1 or caspase-11/4/5, which cleave gasdermin D, separating its N-terminal pore-forming do ... Full text Link to item Cite

Dietary Salt Exacerbates Experimental Colitis.

Journal Article J Immunol · August 1, 2017 The Western diet is characterized by high protein, sugar, fat, and low fiber intake, and is widely believed to contribute to the incidence and pathogenesis of inflammatory bowel disease (IBD). However, high sodium chloride salt content, a defining feature ... Full text Link to item Cite

Programmed cell death as a defence against infection.

Journal Article Nat Rev Immunol · March 2017 Eukaryotic cells can die from physical trauma, which results in necrosis. Alternatively, they can die through programmed cell death upon the stimulation of specific signalling pathways. In this Review, we discuss the role of different cell death pathways i ... Full text Link to item Cite

Loss of Bladder Epithelium Induced by Cytolytic Mast Cell Granules.

Journal Article Immunity · December 20, 2016 Programmed death and shedding of epithelial cells is a powerful defense mechanism to reduce bacterial burden during infection but this activity cannot be indiscriminate because of the critical barrier function of the epithelium. We report that during cysti ... Full text Link to item Cite

IL-1β, IL-18, and eicosanoids promote neutrophil recruitment to pore-induced intracellular traps following pyroptosis.

Journal Article Eur J Immunol · December 2016 Inflammasomes activate caspase-1, initiating a lytic form of programmed cell death termed pyroptosis, which is an important innate immune defense mechanism against intracellular infections. We recently demonstrated in a mouse infection model of pyroptosis ... Full text Link to item Cite

Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis.

Journal Article J Exp Med · September 19, 2016 Inflammasomes activate caspase-1 in response to cytosolic contamination or perturbation. This inflammatory caspase triggers the opening of the GSDMD pore in the plasma membrane, resulting in lytic cell death called pyroptosis. We had previously assumed tha ... Full text Link to item Cite

The Prostaglandin E2-EP3 Receptor Axis Regulates Anaplasma phagocytophilum-Mediated NLRC4 Inflammasome Activation.

Journal Article PLoS Pathog · August 2016 Rickettsial agents are sensed by pattern recognition receptors but lack pathogen-associated molecular patterns commonly observed in facultative intracellular bacteria. Due to these molecular features, the order Rickettsiales can be used to uncover broader ... Full text Link to item Cite

Reassessing the Evolutionary Importance of Inflammasomes.

Journal Article J Immunol · February 1, 2016 Inflammasomes monitor the cytosol for microbial contamination or perturbation and, thus, are predicted to provide potent defense against infection. However, the compendium of data from murine infection models suggests that inflammasomes merely delay the co ... 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 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

Inflammasomes Coordinate Pyroptosis and Natural Killer Cell Cytotoxicity to Clear Infection by a Ubiquitous Environmental Bacterium.

Journal Article Immunity · November 17, 2015 Defective neutrophils in patients with chronic granulomatous disease (CGD) cause susceptibility to extracellular and intracellular infections. Microbes must first be ejected from intracellular niches to expose them to neutrophil attack, so we hypothesized ... 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

Pyroptotic cell death defends against intracellular pathogens.

Journal Article Immunol Rev · May 2015 Inflammatory caspases play a central role in innate immunity by responding to cytosolic signals and initiating a twofold response. First, caspase-1 induces the activation and secretion of the two prominent pro-inflammatory cytokines, interleukin-1β (IL-1β) ... Full text Link to item Cite

Yersinia pestis activates both IL-1β and IL-1 receptor antagonist to modulate lung inflammation during pneumonic plague.

Journal Article PLoS Pathog · March 2015 Pneumonic plague is the most rapid and lethal form of Yersinia pestis infection. Increasing evidence suggests that Y. pestis employs multiple levels of innate immune evasion and/or suppression to produce an early "pre-inflammatory" phase of pulmonary infec ... Full text Link to item Cite

WildCARDs: inflammatory caspases directly detect LPS.

Journal Article Cell Res · February 2015 Inflammasomes are sensors that serve as activation platforms for caspase-1 - a mechanism that set the prevailing paradigm for inflammatory caspase activation. A recent Nature paper by Shi et al. upends this paradigm by describing an unprecedented model for ... Full text Link to item Cite

The RIP1-RIP3 complex initiates mitochondrial fission to fuel NLRP3.

Journal Article Nat Immunol · December 2014 Vesicular stomatitis virus, a single-stranded RNA virus, triggers activation of the serine-threonine kinases RIP1 and RIP3, which damages mitochondria by activating the GTPase DRP1. This results in excessive production of reactive oxygen species and subseq ... Full text Link to item Cite

NAIP inflammasomes give the NOD to bacterial ligands.

Journal Article Trends Immunol · November 2014 NLRs are innate immune sensors that monitor the sanctity of the cytosolic compartment. In a recent paper in Molecular Cell, Tenthorey et al. reveal a novel ligand-sensing interface within regions of the oligomerization domain of the NAIPs, rather than with ... Full text Link to item Cite

NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis.

Journal Article PLoS Negl Trop Dis · September 2014 Burkholderia pseudomallei causes the tropical infection melioidosis. Pneumonia is a common manifestation of melioidosis and is associated with high mortality. Understanding the key elements of host defense is essential to developing new therapeutics for me ... 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 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

miniMAVS, You Complete Me!

Journal Article Cell · February 13, 2014 The functional significance of protein diversification through translational regulation in mammals is largely unexplored. Brubaker et al. now describe the generation of two functionally distinct mammalian proteins, MAVS and miniMAVS, from a single bicistro ... Full text Link to item Cite

Detection of cytosolic bacteria by inflammatory caspases.

Journal Article Curr Opin Microbiol · February 2014 The sanctity of the cytosolic compartment is rigorously maintained by a number of innate immune mechanisms. Inflammasomes detect signatures of microbial infection and trigger caspase-1 or caspase-11 activation, culminating in cytokine secretion and obliter ... Full text Link to item Cite

Salmonella typhimurium impedes innate immunity with a mast-cell-suppressing protein tyrosine phosphatase, SptP.

Journal Article Immunity · December 12, 2013 The virulence of Salmonella is linked to its invasive capacity and suppression of adaptive immunity. This does not explain, however, the rapid dissemination of the pathogen after it breaches the gut. In our study, S. Typhimurium suppressed degranulation of ... Full text Link to item Cite

Cutting edge: Mouse NAIP1 detects the type III secretion system needle protein.

Journal Article J Immunol · October 15, 2013 The NAIP/NLRC4 inflammasomes activate caspase-1 in response to bacterial type III secretion systems (T3SSs). Inadvertent injection of the T3SS rod protein and flagellin into the cytosol is detected through murine NAIP2 and NAIP5/6, respectively. In this st ... Full text Link to item Cite

Mechanisms of NOD-like receptor-associated inflammasome activation.

Journal Article Immunity · September 19, 2013 A major function of a subfamily of NLR (nucleotide-binding domain, leucine-rich repeat containing, or NOD-like receptor) proteins is in inflammasome activation, which has been implicated in a multitude of disease models and human diseases. This work will h ... Full text Link to item Cite

Cytoplasmic LPS activates caspase-11: implications in TLR4-independent endotoxic shock.

Journal Article Science · September 13, 2013 Inflammatory caspases, such as caspase-1 and -11, mediate innate immune detection of pathogens. Caspase-11 induces pyroptosis, a form of programmed cell death, and specifically defends against bacterial pathogens that invade the cytosol. During endotoxemia ... Full text Link to item Cite

Inflammasome-mediated pyroptotic and apoptotic cell death, and defense against infection.

Journal Article Curr Opin Microbiol · June 2013 Cell death is an effective strategy to limit intracellular infections. Canonical inflammasomes, including NLRP3, NLRC4, and AIM2, recruit and activate caspase-1 in response to a range of microbial stimuli and endogenous danger signals. Caspase-1 then promo ... Full text Link to item Cite

Caspase-11 protects against bacteria that escape the vacuole.

Journal Article Science · February 22, 2013 Caspases are either apoptotic or inflammatory. Among inflammatory caspases, caspase-1 and -11 trigger pyroptosis, a form of programmed cell death. Whereas both can be detrimental in inflammatory disease, only caspase-1 has an established protective role du ... Full text Link to item Cite

Detection of pyroptosis by measuring released lactate dehydrogenase activity.

Journal Article Methods Mol Biol · 2013 Pyroptosis is a form of programmed, inflammatory cell death that is dependent on the activation of a cysteine protease caspase-1. Following caspase-1 activation via inflammasomes (including NLRP3, NLRC4, Nlrp1b, and AIM2), cells lose membrane integrity and ... Full text Link to item Cite

Just say NO to NLRP3.

Journal Article Nat Immunol · January 2013 Full text Link to item Cite

YopM puts caspase-1 on ice.

Journal Article Cell Host Microbe · December 13, 2012 Caspase-1-mediated detection of pathogens is a potent arm of the innate immune system. LaRock and Cookson (2012) show that the Yersinia type III secretion effector, YopM, directly inhibits caspase-1. ... Full text Link to item Cite

Interferon-β therapy against EAE is effective only when development of the disease depends on the NLRP3 inflammasome.

Journal Article Sci Signal · May 22, 2012 Interferon-β (IFN-β) is widely used to treat multiple sclerosis (MS), and its efficacy was demonstrated in the setting of experimental autoimmune encephalomyelitis (EAE), an animal model of MS; however, IFN-β is not effective in treating all cases of MS. H ... Full text Link to item Cite

Caspase-1-induced pyroptotic cell death.

Journal Article Immunol Rev · September 2011 Programmed cell death is a necessary part of development and tissue homeostasis enabling the removal of unwanted cells. In the setting of infectious disease, cells that have been commandeered by microbial pathogens become detrimental to the host. When macr ... Full text Link to item Cite

Generation of a Listeria vaccine strain by enhanced caspase-1 activation.

Journal Article Eur J Immunol · July 2011 The immunostimulatory properties conferred by vaccine adjuvants require caspase-1 for processing of IL-1β and IL-18. Caspase-1 is activated in response to a breach of the cytosolic compartment by microbes and the process is initiated by intracellular patte ... Full text Link to item Cite

The NLRP3 inflammasome detects encephalomyocarditis virus and vesicular stomatitis virus infection.

Journal Article J Virol · May 2011 Inflammasomes are cytosolic protein complexes that regulate caspase-1 activation and the secretion of interleukin-1β (IL-1β) and IL-18. Several different inflammasome complexes have been identified, but the NLRP3 inflammasome is particularly notable becaus ... Full text Link to item Cite

Differential requirements for NAIP5 in activation of the NLRC4 inflammasome.

Journal Article Infect Immun · April 2011 Inflammasomes are cytosolic multiprotein complexes that assemble in response to infectious or noxious stimuli and activate the CASPASE-1 protease. The inflammasome containing the nucleotide binding domain-leucine-rich repeat (NBD-LRR) protein NLRC4 (interl ... Full text Link to item Cite

Salmonella and Caspase-1: A complex Interplay of Detection and Evasion.

Journal Article Front Microbiol · 2011 Salmonellae are intracellular pathogens that replicate within epithelial cells and macrophages, and are a significant public health threat in both developed and developing countries. The innate immune system detects microbes through pattern recognition rec ... Full text Link to item Cite

Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria.

Journal Article Nat Immunol · December 2010 Macrophages mediate crucial innate immune responses via caspase-1-dependent processing and secretion of interleukin 1β (IL-1β) and IL-18. Although infection with wild-type Salmonella typhimurium is lethal to mice, we show here that a strain that persistent ... Full text Link to item Cite

Activation of the NLRP3 inflammasome by intracellular poly I:C.

Journal Article FEBS Lett · November 19, 2010 Several RNA viruses can be detected by the inflammasome, which promotes IL-1β and IL-18 secretion, but the underlying mechanisms of detection remain unclear. Cytosolic dsRNA is a replication intermediate of many RNA viruses. We show here that transfection ... Full text Link to item Cite

Cutting edge: Cytosolic bacterial DNA activates the inflammasome via Aim2.

Journal Article J Immunol · July 15, 2010 Pathogens are detected by pattern recognition receptors that, upon activation, orchestrate an appropriate immune response. The TLRs and the nucleotide-binding oligomerization domain-like receptors (NLRs) are prototypic pattern recognition receptors that de ... Full text Link to item Cite

Innate immune detection of bacterial virulence factors via the NLRC4 inflammasome.

Journal Article J Clin Immunol · July 2010 INTRODUCTION: Cytokine production by innate immune cells is initiated by signaling downstream of pattern recognition receptors, including Toll-like receptors. DISCUSSION: A subset of cytokines, including IL-1beta and IL-18, require post-translational prote ... Full text Link to item Cite

Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome.

Journal Article Proc Natl Acad Sci U S A · February 16, 2010 The mammalian innate immune system uses Toll-like receptors (TLRs) and Nod-LRRs (NLRs) to detect microbial components during infection. Often these molecules work in concert; for example, the TLRs can stimulate the production of the proforms of the cytokin ... Full text Link to item Cite

Staphylococcus aureus evades lysozyme-based peptidoglycan digestion that links phagocytosis, inflammasome activation, and IL-1beta secretion.

Journal Article Cell Host Microbe · January 21, 2010 IL-1beta produced by phagocytes is important for protection against the mucosal pathogen Staphylococcus aureus. Processing and maturation of this cytokine requires activation of the multiprotein inflammasome complex. We observed that the bacterial cell wal ... Full text Link to item Cite

Virus binding to a plasma membrane receptor triggers interleukin-1 alpha-mediated proinflammatory macrophage response in vivo.

Journal Article Immunity · July 17, 2009 The recognition of viral components by host pattern-recognition receptors triggers the induction of the antiviral innate immune response. Toll-like receptor 9 (TLR9) and NLRP3 inflammasome were shown to be the principal specific sensors of viral double-str ... Full text Link to item Cite

Multiple Nod-like receptors activate caspase 1 during Listeria monocytogenes infection.

Journal Article J Immunol · June 1, 2008 Listeria monocytogenes escapes from the phagosome of macrophages and replicates within the cytosolic compartment. The macrophage responds to L. monocytogenes through detection pathways located on the cell surface (TLRs) and within the cytosol (Nod-like rec ... Full text Link to item Cite

Pseudomonas aeruginosa activates caspase 1 through Ipaf.

Journal Article Proc Natl Acad Sci U S A · February 19, 2008 The innate immune system encodes cytosolic Nod-like receptors (NLRs), several of which activate caspase 1 processing and IL-1beta and IL-18 secretion. Macrophages respond to Salmonella typhimurium infection by activating caspase 1 through the NLR Ipaf. Thi ... Full text Link to item Cite

TLR5 and Ipaf: dual sensors of bacterial flagellin in the innate immune system.

Journal Article Semin Immunopathol · September 2007 The innate immune system precisely modulates the intensity of immune activation in response to infection. Flagellin is a microbe-associated molecular pattern that is present on both pathogenic and nonpathogenic bacteria. Macrophages and dendritic cells are ... Full text Link to item Cite

Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf.

Journal Article Nat Immunol · June 2006 Macrophages respond to Salmonella typhimurium infection via Ipaf, a NACHT-leucine-rich repeat family member that activates caspase-1 and secretion of interleukin 1beta. However, the specific microbial salmonella-derived agonist responsible for activating I ... Full text Link to item Cite

Salmonella effectors translocated across the vacuolar membrane interact with the actin cytoskeleton.

Journal Article Mol Microbiol · April 2003 A family of nine Salmonella typhimurium type III secretion effectors with a conserved amino-terminus have been defined. Three family members (SifA, SifB and SseJ) have previously been demonstrated to localize to the Salmonella-containing vacuole and to Sal ... Full text Link to item Cite

Transcription of the SsrAB regulon is repressed by alkaline pH and is independent of PhoPQ and magnesium concentration.

Journal Article J Bacteriol · March 2002 The Salmonella pathogenicity island 2 (SPI-2) type III secretion system is expressed by intracellular bacteria and translocates effector proteins across the vacuolar membrane. Signals sensed by Salmonella enterica serovar Typhimurium in the intracellular c ... Full text Link to item Cite

InvB is a type III secretion chaperone specific for SspA.

Journal Article J Bacteriol · December 2000 A wide variety of gram-negative bacteria utilize a specialized apparatus called the type III secretion system (TTSS) to translocate virulence factors directly into the cytoplasm of eukaryotic cells. These translocated effectors contribute to the pathogen's ... Full text Link to item Cite

A conserved amino acid sequence directing intracellular type III secretion by Salmonella typhimurium.

Journal Article Proc Natl Acad Sci U S A · June 20, 2000 Type III secretion systems (TTSS) are important virulence factors that Gram-negative bacteria use to translocate proteins into the cytoplasm of eukaryotic host cells. Salmonellae encode two virulence-associated TTSS. The Salmonella pathogenicity island 1 ( ... Full text Link to item Cite

Identification of a putative Salmonella enterica serotype typhimurium host range factor with homology to IpaH and YopM by signature-tagged mutagenesis.

Journal Article Infect Immun · December 1999 The genetic basis for the host adaptation of Salmonella serotypes is currently unknown. We have explored a new strategy to identify Salmonella enterica serotype Typhimurium (S. typhimurium) genes involved in host adaptation, by comparing the virulence of 2 ... Full text Link to item Cite

Salmonella typhimurium leucine-rich repeat proteins are targeted to the SPI1 and SPI2 type III secretion systems.

Journal Article Mol Microbiol · November 1999 Salmonellae encode two virulence-associated type III secretion systems (TTSS) within Salmonella pathogenicity islands 1 and 2 (SPI1 and SPI2). Two Salmonella typhimurium genes, sspH1 and sspH2, that encode proteins similar to the Shigella flexneri and Yers ... Full text Link to item Cite

Bacteriophages in the evolution of pathogen-host interactions.

Journal Article Proc Natl Acad Sci U S A · August 17, 1999 Full text Link to item Cite