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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Nitric Oxide Engages an Anti-inflammatory Feedback Loop Mediated by Peroxiredoxin 5 in Phagocytes.
Daniel B. Graham,Guadalupe J. Jasso,Guadalupe J. Jasso,Amanda Mok,Gautam Goel,Aylwin Ng,Raivo Kolde,Mukund Varma,John G. Doench,David E. Root,Clary B. Clish,Steven A. Carr,Ramnik J. Xavier +12 more
TL;DR: It is demonstrated that engaging the antioxidant response is sufficient to suppress Toll-like receptor (TLR)-induced cytokine production in dendritic cells and that Prdx5 is required for attenuation of inflammatory cytokineproduction.
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Targeting immunometabolism in host defence against Mycobacterium tuberculosis
TL;DR: This review aims to examine the metabolic demands of the immune cells involved in both host resistance and disease tolerance, chiefly the macrophage and T‐lymphocyte, and discusses how baseline metabolic heterogeneity and inflammation‐driven metabolic reprogramming during infection are linked to their key immune functions.
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Research Progress on the Role of Inflammasomes in Kidney Disease.
TL;DR: The research progress oninflammasomes and the key pathogenic roles of inflammasome in the development and progression of kidney diseases are focused on and the potential of this intracellular inflammation to further prevent or block the development of the kidney disease is explored.
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Conversion of human M-CSF macrophages into foam cells reduces their proinflammatory responses to classical M1-polarizing activation.
Rafaela F. da Silva,Rafaela F. da Silva,Jani Lappalainen,Miriam Lee-Rueckert,Petri T. Kovanen +4 more
TL;DR: Conversion of cultured human macrophages into foam cells suppresses their proinflammatory responses to M1-polarizing factors, which may locally weaken the macrophage-dependent inflammatory component of atherogenesis.
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Phosphodiesterase 3B (PDE3B) regulates NLRP3 inflammasome in adipose tissue.
Faiyaz Ahmad,Youn Wook Chung,Yan Tang,Steven Hockman,Shiwei Liu,Yusuf Khan,Kevin Huo,Eric M. Billings,Marcelo Amar,Alan T. Remaley,Vincent C. Manganiello +10 more
TL;DR: A role for PDE3B in modulating inflammatory response is established, which may contribute to a reduced inflammatory state in adipose tissue.
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.
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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.