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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Immune evasion and provocation by Mycobacterium tuberculosis
TL;DR: Chandra et al. as mentioned in this paper discuss immune evasion and provocation by M. tuberculosis during its infection cycle and describe how a more detailed molecular understanding is crucial to enable the development of novel host-directed therapies, disease biomarkers and effective vaccines.
Journal ArticleDOI
Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic surveillance systems and modulates IL-1β production.
Jeremy Sousa,Jeremy Sousa,Baltazar Cá,Baltazar Cá,Ana Raquel Maceiras,Ana Raquel Maceiras,Luisa Simoes-Costa,Luisa Simoes-Costa,Kaori L. Fonseca,Kaori L. Fonseca,Ana Isabel Rodrigues Fernandes,Ana Isabel Rodrigues Fernandes,Angélica Ramos,Teresa Carvalho,Leandro Barros,Leandro Barros,Carlos Magalhães,Álvaro Chiner-Oms,Henrique Machado,Maria Isabel Veiga,Albel Singh,Rui Pereira,Rui Pereira,António Amorim,António Amorim,Jorge Vieira,Jorge Vieira,Cristina P. Vieira,Cristina P. Vieira,Apoorva Bhatt,Fernando Rodrigues,Pedro Rodrigues,Pedro Rodrigues,Sebastien Gagneux,Sebastien Gagneux,António G. Castro,João Tiago Guimarães,Helder Novais Bastos,Nuno S. Osório,Iñaki Comas,Margarida Saraiva,Margarida Saraiva +41 more
TL;DR: Evidence is provided that M. tuberculosis strains manipulate host-pathogen interactions to drive variable TB severities by stratifying patients by severity of tuberculosis and finding correlations with the level of IL-1β production by macrophages exposed to these isolates.
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Pyroptosis is a critical immune-inflammatory response involved in atherosclerosis.
TL;DR: In this article, the authors focus on the pathogenesis, influence, and therapy of pyroptosis in atherosclerosis and provide novel ideas for suppressing pyroplosis and the progression of atheros sclerosis.
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Redox-signals and macrophage biology.
Andreas Weigert,Andreas von Knethen,Dominik C. Fuhrmann,Nathalie Dehne,Bernhard Brüne,Bernhard Brüne +5 more
TL;DR: Macrophage responses in terms of nitric oxide and superoxide formation with the modulating impact of hypoxia are discussed, and the role of redox-signaling affecting epigenetics is summarized and the central role of mitochondrial-derived oxygen species in inflammation is reflected.
Journal ArticleDOI
Targeting NLRP3 Inflammasome Activation in Severe Asthma
TL;DR: An overview of the pathophysiology of SA is provided, molecular mechanisms underlying aberrant inflammatory responses in the airways are presented, and the potential of targeting NLRP3 as a novel therapeutic approach for the management of asthma is contemplated.
References
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