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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The E3 Ubiquitin Ligase TRIM65 Negatively Regulates Inflammasome Activation Through Promoting Ubiquitination of NLRP3.
TL;DR: In this paper, the effects of Tripartite motif-containing protein 65 (TRIM65) on NLRP3 inflammasome activation and the underlying molecular mechanism were investigated in vitro and in vivo.
Journal ArticleDOI
Functional characterization of receptor-interacting serine/threonine kinase 2 (RIP2) of the goldfish (Carassius auratus L.).
Jiasong Xie,Miodrag Belosevic +1 more
TL;DR: The results of dual luciferase reporter assay revealed that RIP2 over-expression caused the activation of the NF-κB signal pathway and RIP2 was involved in the regulation of the production of TNFα-2 and IL-1β1 in goldfish macrophages exposed to M. marinum.
Journal ArticleDOI
NLRP3, un inflammasome sous contrôle
TL;DR: Cette revue presente les avancees sur the signalisation du priming (ou amorcage) du complexe puis of son activation avec une attention particuliere sur le role des modifications post-traductionnelles de NLRP3.
Journal ArticleDOI
Andrographolide exerts anti-inflammatory effects in Mycobacterium tuberculosis-infected macrophages by regulating the Notch1/Akt/NF-κB axis
TL;DR: Results showed that Andro inhibits the production of IL‐1β and other inflammatory cytokines in a dose‐dependent manner, and Andro has been found to suppress the Notch1/Akt/NF‐κB signaling pathway.
Journal ArticleDOI
FX11 limits Mycobacterium tuberculosis growth and potentiates bactericidal activity of isoniazid through host-directed activity.
Gopinath Krishnamoorthy,Peggy Kaiser,Ulrike Abu Abed,January Weiner,Pedro Moura-Alves,Pedro Moura-Alves,Volker Brinkmann,Stefan H. E. Kaufmann,Stefan H. E. Kaufmann +8 more
TL;DR: Targeting LDHA results in tumor regression in experimental models and co-administration of a known small molecule LDHA inhibitor and an anti-tuberculosis drug has improved the tuberculosis therapeutic outcomes in murine models.
References
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Journal ArticleDOI
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Journal ArticleDOI
AIM2 recognizes cytosolic dsDNA and forms a caspase-1 activating inflammasome with ASC
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TL;DR: Using mouse and human cells, the PYHIN (pyrin and HIN domain-containing protein) family member absent in melanoma 2 (AIM2) is identified as a receptor for cytosolic DNA, which regulates caspase-1.
Journal ArticleDOI
Erratum: NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals (Nature (2010) 464 (1357-1361))
Peter Duewell,Hajime Kono,Katey J. Rayner,Cherilyn M. Sirois,Gregory I. Vladimer,Franz Bauernfeind,George S. Abela,Luigi Franchi,Gabriel Núñez,Max Schnurr,Terje Espevik,Egil Lien,Katherine A. Fitzgerald,Kenneth L. Rock,Kathryn J. Moore,Samuel D. Wright,Veit Hornung,Eicke Latz +17 more
TL;DR: This corrects the article to show that the method used to derive the H2O2 “spatially aggregating force” is a two-step process, not a single step, like in the previous version of this paper.
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