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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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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The Role of Post-Translational Modifications in Regulation of NLRP3 Inflammasome Activation
TL;DR: In this article , a review of post-translational modifications of the components of the NLRP3 inflammasome and the resultant effects on regulation of its activity is presented.
Journal ArticleDOI
Relevance of inducible nitric oxide synthase for immune control of Mycobacterium avium subspecies paratuberculosis infection in mice.
Ketema Abdissa,Nanthapon Ruangkiattikul,Wiebke Ahrend,Andreas Nerlich,Andreas Beineke,Kristin Laarmann,Nina Janze,Ulrike Lobermeyer,Abdulhadi Suwandi,Christine S. Falk,Ulrike Schleicher,Siegfried Weiss,Christian Bogdan,Ralph Goethe +13 more
TL;DR: A strong T cell response and concomitant NOS2/NO activity appears to control MAP infection, but allows development of chronicity and pathogen persistence in ruminants.
Posted ContentDOI
Genetic modification of inflammation and clonal hematopoiesis-associated coronary artery disease
Z. Yu,Trevor P. Fidler,Yan Ruan,Caitlyn Vlasschaert,Takaharu Nakao,M. Uddin,T. Mack,Abhishek Niroula,Jonathan Brett Heimlich,Seyedeh M. Zekavat,Christopher J. Gibson,Georgia Griffin,Y. Wang,Gina M. Peloso,Nancy L. Heard-Costa,Daniel Levy,Ramachandran S. Vasan,François Aguet,Kristin G. Ardlie,Kent D. Taylor,Stephen S. Rich,J. Rotter,Peter Libby,Siddhartha Jaiswal,Benjamin L. Ebert,Alexander G. Bick,Alan R. Tall,Prasad Natarajan +27 more
TL;DR: In this paper , an inflammatory gene modifier scan for CHIP-associated CVD risk among 424,651 UK Biobank participants was carried out to identify CHIP associated with an increased risk of cardiovascular diseases (CVD) via inflammasome activation.
Journal ArticleDOI
Histone deacetylase-2 controls IL-1β production through the regulation of NLRP3 expression and activation in tuberculosis infection
TL;DR: In this paper , the authors found that HDAC inhibitor, 4-(dimethylamino)-N-[6-(hydroxyamino)-6-oxohexyl]-benzamide (DHOB), enhanced IL-1β production by macrophage and dendritic cells upon TLR4 stimulation or Mycobacterium tuberculosis infection through elevated NLRP3 expression, increased cleaved caspase-1, and enhanced ASC oligomerization.
current TB vaccine candidates. However, given the recent failures of such a TB vaccine candidate in clinical trials, strategies to harness CD4-independent mechanisms of protection should be included in future vaccine design. Here, we have reported that noncognate IFN-γ production by Mtb antigen-independent memory CD8
TL;DR: In this article, the authors provided a comprehensive mechanistic framework for antigen-independent IFN-γ secretion in response to Mtb with critical implications for future intervention strategies against TB.
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