Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome-dependent processing of IL-1β.
Bibhuti B. Mishra,Vijay A. K. Rathinam,Gregory W. Martens,Amanda J. Martinot,Hardy Kornfeld,Katherine A. Fitzgerald,Christopher M. Sassetti,Christopher M. Sassetti +7 more
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TLDR
By exogenously controlling the replication of Mycobacterium tuberculosis in vivo, the requirement for antimicrobial immunity is obviated and it is discovered that both IL-1 production and infection-induced immunopathology were suppressed by lymphocyte-derived interferon-γ (IFN-γ).Abstract:
Interleukin 1 (IL-1) is an important mediator of innate immunity but can also promote inflammatory tissue damage. During chronic infections such as tuberculosis, the beneficial antimicrobial role of IL-1 must be balanced with the need to prevent immunopathology. By exogenously controlling the replication of Mycobacterium tuberculosis in vivo, we obviated the requirement for antimicrobial immunity and discovered that both IL-1 production and infection-induced immunopathology were suppressed by lymphocyte-derived interferon-γ (IFN-γ). This effect was mediated by nitric oxide (NO), which we found specifically inhibited assembly of the NLRP3 inflammasome via thiol nitrosylation. Our data indicate that the NO produced as a result of adaptive immunity is indispensable in modulating the destructive innate inflammatory responses elicited during persistent infections.read more
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Activation and regulation of the inflammasomes
TL;DR: The complex regulatory mechanisms that facilitate a balanced but effective inflammasome-mediated immune response are discussed, and the similarities to another molecular signalling platform — the apoptosome — that monitors cellular health are highlighted.
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Inflammasomes: mechanism of assembly, regulation and signalling
Petr Broz,Vishva M. Dixit +1 more
TL;DR: This Review discusses the recent developments in inflammasome research with a focus on the molecular mechanisms that govern inflammaome assembly, signalling and regulation.
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The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation.
TL;DR: Current understanding of the mechanisms ofNLRP3 inflammasome activation by multiple signaling events, and its regulation by post-translational modifications and interacting partners of NLRP3 are summarized.
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Regulation of inflammasome activation
TL;DR: Genetic studies indicate that mutations in NLRP1, NLRP3, NLRC4, and AIM2 are linked with the development of auto‐inflammatory diseases, enterocolitis, and cancer and transform the understanding of the basic biology and clinical relevance of inflammasomes.
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Dopamine Controls Systemic Inflammation through Inhibition of NLRP3 Inflammasome
TL;DR: DA and DRD1 signaling prevent NLRP3 inflammasome-dependent inflammation, including neurotoxin-induced neuroinflammation, LPS-induced systemic inflammation, and monosodium urate crystal (MSU)-induced peritoneal inflammation.
References
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Neutrophil Responses to Mycobacterium tuberculosis Infection in Genetically Susceptible and Resistant Mice
Evgenyi B. Eruslanov,Irina V. Lyadova,Tatiana Kondratieva,Konstantin B. Majorov,Ilya V. Scheglov,Marianna Orlova,Alexander S. Apt +6 more
TL;DR: It is shown that mice of the I/St strain which are genetically susceptible to TB show an unusually high and prolonged neutrophil accumulation in their lungs after intratracheal infection, and that neutrophils may play the role of a “Trojan horse” for mycobacteria.
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Superoxide dismutase 1 regulates caspase-1 and endotoxic shock
TL;DR: It is shown that superoxide dismutase 1 (SOD1) regulates caspase-1 activation and in SOD1-deficient macrophages, higher superoxide production decreased the cellular redox potential and specifically inhibited casp enzyme-1 by reversible oxidation and glutathionylation of the redox-sensitive cysteine residues Cys397 and Cys362.
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NOD2, RIP2 and IRF5 play a critical role in the type I interferon response to Mycobacterium tuberculosis.
Amit K. Pandey,Yibin Yang,Zhaozhao Jiang,Sarah M. Fortune,François Coulombe,Marcel A. Behr,Katherine A. Fitzgerald,Christopher M. Sassetti,Michelle A. Kelliher +8 more
TL;DR: The Nod2 system is specialized to recognize bacteria that actively perturb host membranes and is remarkably sensitive to mycobacteria, perhaps reflecting the strong evolutionary pressure exerted by these pathogens on the mammalian immune system.
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Early granuloma formation after aerosol Mycobacterium tuberculosis infection is regulated by neutrophils via CXCR3‐signaling chemokines
Peter Seiler,Peter Aichele,Silke Bandermann,Anja E. Hauser,Bao Lu,Norma P. Gerard,Craig Gerard,Stefan Ehlers,Hans J. Mollenkopf,Stefan H. E. Kaufmann +9 more
TL;DR: It is reported that PMN are essential for accurate early granuloma formation during chronic M. tuberculosis infection without influencing mycobacterial growth restriction.
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Assessment and Application of the Biotin Switch Technique for Examining Protein S-Nitrosylation under Conditions of Pharmacologically Induced Oxidative Stress
TL;DR: Combining BST with photolysis has shown that anti-cancer drug-induced oxidative stress facilitates the S-nitrosylation of the major apoptotic effector glyceraldehyde-3-phosphate dehydrogenase, and demonstrated that SNO-dependent signaling pathways can be modulated by oxidative conditions.