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 in Macrophage Immunometabolism: Hiding in Plain Sight
TL;DR: Findings indicating that NO, through its interaction with heme and non-heme metal containing proteins, together with components of the electron transport chain, functions not only as a regulator of cell respiration, but also a modulator of intracellular cell metabolism are reviewed.
Journal ArticleDOI
TXNIP Deficiency Exacerbates Endotoxic Shock via the Induction of Excessive Nitric Oxide Synthesis
Young-Jun Park,Sung-Jin Yoon,Sung-Jin Yoon,Hyun-Woo Suh,Dong Oh Kim,Dong Oh Kim,Jeong-Ran Park,Haiyoung Jung,Haiyoung Jung,Tae-Don Kim,Tae-Don Kim,Suk Ran Yoon,Suk Ran Yoon,Jeong-Ki Min,Jeong-Ki Min,Hee-Jun Na,Seon-Jin Lee,Hee Gu Lee,Young Ho Lee,Hee-Bong Lee,Inpyo Choi,Inpyo Choi +21 more
TL;DR: It is demonstrated that Txnip−/− mice are significantly more susceptible to lipopolysaccharide (LPS)-induced endotoxic shock, and TXNIP is a novel molecule that links NO synthesis and NLRP3 inflammasome activation during endotoxicshock.
Journal ArticleDOI
Posttranslational Modification as a Critical Determinant of Cytoplasmic Innate Immune Recognition
Paul J. Baker,Paul J. Baker,Dominic De Nardo,Dominic De Nardo,Fiona Moghaddas,Fiona Moghaddas,Le Son Tran,Le Son Tran,Annabell Bachem,Annabell Bachem,Trang Nguyen,Trang Nguyen,Thomas J. Hayman,Thomas J. Hayman,Hazel Tye,Hazel Tye,James E Vince,James E Vince,Sammy Bedoui,Sammy Bedoui,Richard L. Ferrero,Richard L. Ferrero,Seth L. Masters,Seth L. Masters +23 more
TL;DR: Significant changes in key intracellular processes such as phosphorylation, ubiquitination, and other pathways leading to posttranslational protein modification are key determinants of innate immune recognition in the cytoplasm.
Journal ArticleDOI
The Immune Mechanisms of Lung Parenchymal Damage in Tuberculosis and the Role of Host-Directed Therapy.
Cari Stek,Brian W. Allwood,Naomi F. Walker,Naomi F. Walker,Robert J. Wilkinson,Lutgarde Lynen,Graeme Meintjes +6 more
TL;DR: The different features of TB immunopathology that lead to impaired lung function, namely cavities, bronchiectasis, and fibrosis are described, and various existing drugs that affect one or more of the immunological mediators of lung damage and could therefore play a role as host-directed therapy are focused on.
Journal ArticleDOI
Inflammasome Activation Underlying Central Nervous System Deterioration in HIV-Associated Tuberculosis.
Suzaan Marais,Rachel P.J. Lai,Katalin A. Wilkinson,Katalin A. Wilkinson,Graeme Meintjes,Anne O'Garra,Anne O'Garra,Robert J. Wilkinson,Robert J. Wilkinson,Robert J. Wilkinson +9 more
TL;DR: W Whole-blood transcriptome findings complement protein measurement from the site of disease, which together suggest a dominant role for the innate immune system in the pathogenesis of TBM-IRIS.
References
More filters
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.