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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Parkin deficiency modulates NLRP3 inflammasome activation by attenuating an A20-dependent negative feedback loop.
François Mouton-Liger,Thibault Rosazza,Julia E. Sepulveda-Diaz,Amélie Ieang,Sidi-Mohamed Hassoun,Emilie Claire,Graziella Mangone,Alexis Brice,Patrick P. Michel,Jean-Christophe Corvol,Olga Corti +10 more
TL;DR: The observations suggest that the A20/NLRP3‐inflammasome axis participates in the pathogenesis of PARK2‐linked PD, paving the way for the exploration of its potential as a biomarker and treatment target.
Journal ArticleDOI
Macrophage form, function, and phenotype in mycobacterial infection: lessons from tuberculosis and other diseases.
TL;DR: This review highlights how distinct macrophage phenotypes may influence disease progression in tuberculosis and draws on work investigating specializedmacrophage populations important in cancer biology and atherosclerosis in order to suggest new areas of investigation relevant to mycobacterial pathogenesis.
Journal ArticleDOI
Autophagy as an immune effector against tuberculosis
Steven B. Bradfute,Eliseo F. Castillo,John Arko-Mensah,Santosh Chauhan,Shanya Jiang,Michael A. Mandell,Vojo Deretic +6 more
TL;DR: Genome wide association studies indicate a considerable overlap between autophagy, human susceptibility to mycobacterial infections and predisposition loci for inflammatory bowel disease, and recent studies show that Autophagy is an important regulator and effector of IL-1 responses, and that autphagy intersects with type I interferon pathology-modulating responses.
Journal ArticleDOI
NLRP3 inflammasome and host protection against bacterial infection.
J.W. Kim,Eun-Kyeong Jo +1 more
TL;DR: The current knowledge of the roles and regulation of the NLRP3 inflammasome during bacterial infections is discussed and potential treatment approaches against pathogenic infections are discussed.
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Nitric Oxide Modulates Macrophage Responses to Mycobacterium tuberculosis Infection through Activation of HIF-1α and Repression of NF-κB.
TL;DR: It is found that iNOS broadly regulates the macrophage transcriptome during M. tuberculosis infection, activating antimicrobial pathways while also limiting inflammatory cytokine production, and that NO inhibits NF-κB activity to prevent hyperinflammatory responses.
References
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