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 NLRP3 inflammasome is a potential mechanism and therapeutic target for perioperative neurocognitive disorders
TL;DR: In this article , a review summarizes recent studies and systematically describes the pathogenesis of NLRP3 activation and regulation and potential therapeutics targeting NLRP-containing protein 3 (NLRP3) inflammasomes in PND patients.
Dissertation
Early macrophage response to Mycobacterium avium subspecies paratuberculosis
TL;DR: This paper presents a meta-analyses of the determinants of infectious disease in eight operation theatres and shows clear patterns in response to treatment-side-of-the-art attacks and in particular the immune systems of mice and birds are affected.
Journal ArticleDOI
A single-cell mathematical model of sars-cov-2 induced pyroptosis and the effects of anti-inflammatory intervention
Sara Hamis,Fiona R Macfarlane +1 more
TL;DR: It is demonstrated that an anti-inflammatory drug can delay the formation of the NLRP3 inflammasome, and thus may alter the mode of cell death from inflammatory (pyroptosis) to non-inflammatory e.g., apoptosis).
Journal ArticleDOI
Endothelial Dysfunction Accelerates Impairment of Mitochondrial Function in Ageing Kidneys via Inflammasome Activation
Yoshihisa Wada,Reina Umeno,Hajime Nagasu,Megumi Kondo,Atsuyuki Tokuyama,Hiroyuki Kadoya,Kengo Kidokoro,Shun'ichiro Taniguchi,Masafumi Takahashi,Tamaki Sasaki,Naoki Kashihara +10 more
TL;DR: In this paper, the role of endothelial dysfunction and the lack of an eNOS-NO pathway in the progression of aged kidneys was elucidated by using both normal and deficient mice.
Posted ContentDOI
Evaluation of IL-1 blockade as a host-directed therapy for tuberculosis in mice and macaques [preprint]
Caylin G. Winchell,Bibhuti B. Mishra,Bibhuti B. Mishra,Samantha J. Nelson,Christopher M. Sassetti,JoAnne L. Flynn +5 more
TL;DR: An HDT to target the IL-1 pathway, an inflammatory immune response that is both critical and detrimental to TB disease outcome, is designed to enhance LZD efficacy by negating LzD-host toxicities and to reduce adverse inflammation caused by TB.
References
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Journal ArticleDOI
Immunological and Inflammatory Functions of the Interleukin-1 Family
TL;DR: The IL-1 family includes members that suppress inflammation, both specifically within the IL-2 family but also nonspecifically for TLR ligands and the innate immune response.
Journal ArticleDOI
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
Peter Duewell,Hajime Kono,Katey J. Rayner,Katey J. Rayner,Cherilyn M. Sirois,Gregory I. Vladimer,Franz Bauernfeind,George S. Abela,Luigi Franchi,Guillermo Gabriel Nuñez,Max Schnurr,Terje Espevik,Egil Lien,Katherine A. Fitzgerald,Kenneth L. Rock,Kathryn J. Moore,Kathryn J. Moore,Samuel D. Wright,Veit Hornung,Eicke Latz,Eicke Latz +20 more
TL;DR: It is shown that cholesterol crystals activate the NLRP3 inflammasome in phagocytes in vitro in a process that involves phagolysosomal damage and that crystalline cholesterol acts as an endogenous danger signal and its deposition in arteries or elsewhere is an early cause rather than a late consequence of inflammation.
Journal ArticleDOI
AIM2 recognizes cytosolic dsDNA and forms a caspase-1 activating inflammasome with ASC
Veit Hornung,Veit Hornung,Andrea Ablasser,Andrea Ablasser,Marie Charrel-Dennis,Franz Bauernfeind,Franz Bauernfeind,Gabor Horvath,Daniel R. Caffrey,Eicke Latz,Katherine A. Fitzgerald +10 more
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.
Journal ArticleDOI
Nitrosylation. the prototypic redox-based signaling mechanism.
TL;DR: Whereas phosphorylation clearly Spain lies at the heart of many signal transduction pathways, has been expanded re-translational modification of proteins, are conserved cently by the discovery of an enzymatic function for throughout evolution and influence most aspects of cel-hemoglobin.