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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Inflammasomes on the Crossroads of Innate Immune Recognition and Metabolic Control
Tomasz Próchnicki,Eicke Latz +1 more
TL;DR: The findings on how microbial- and host-derived metabolites regulate activation of the NLRP3 and NLRP6 inflammasomes are reviewed and the different models of how glycolysis and mitochondrial metabolism control theNLRP3 inflammaome are discussed.
Journal ArticleDOI
Mechanisms and pathways of innate immune activation and regulation in health and cancer
TL;DR: This review focuses on the recent advances in the understanding of the activation and regulation of innate immune signaling in the host response to pathogens and cancer.
Journal ArticleDOI
MicroRNA let-7 Modulates the Immune Response to Mycobacterium tuberculosis Infection via Control of A20, an Inhibitor of the NF-κB Pathway
Manish Kumar,Sanjaya Kumar Sahu,Ranjeet Kumar,Arijita Subuddhi,Ranjan Kumar Maji,Kuladip Jana,Pushpa Gupta,Johanna Raffetseder,Maria Lerm,Zhumur Ghosh,Geert van Loo,Rudi Beyaert,Umesh D. Gupta,Manikuntala Kundu,Joyoti Basu +14 more
TL;DR: A role is uncovered for let-7f and its target A20 in regulating immune responses to Mtb and controlling bacterial burden.
Journal ArticleDOI
Interplay Between NLRP3 Inflammasome and Autophagy.
TL;DR: Inflammasome signaling pathways can regulate autophagic process necessary for balance between required host defense inflammatory response and prevention of excessive and detrimental inflammation, which has a protective role in some inflammatory diseases associated with NLRP3 inflammasomes.
Journal ArticleDOI
Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis.
Bibhuti B. Mishra,Rustin R. Lovewell,Andrew J. Olive,Guoliang Zhang,Wenfei Wang,Eliseo A. Eugenin,Clare M. Smith,Jia Yao Phuah,Jarukit E. Long,Michelle L. Dubuke,Samantha G. Palace,Jon D. Goguen,Richard Baker,Subhalaxmi Nambi,Rabinarayan Mishra,Matthew G. Booty,Christina E. Baer,Scott A. Shaffer,Véronique Dartois,Beth A. McCormick,Xinchun Chen,Christopher M. Sassetti +21 more
TL;DR: The data suggest that M. tuberculosis exploits neutrophilic inflammation to preferentially replicate at sites of tissue damage that promote contagion, and that a similar inflammatory pathway promotes tuberculosis in patients.
References
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