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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Chloroquine/hydroxychloroquine: an inflammasome inhibitor in severe COVID-19?
Mohammad Bahadoram,Bijan Keikhaei,Ali Saeedi-Boroujeni,Ali Saeedi-Boroujeni,Mohammad-Reza Mahmoudian-Sani +4 more
TL;DR: In this paper, the potential inhibitory effect of chloroquine and hydroxychloroquine on inflammasome was surveyed and the role of NLRP3 inhibitors in the treatment of COVID-19 has been considered.
Journal ArticleDOI
Mycobacterium tuberculosis clinical isolates of the Beijing and East-African Indian lineage induce fundamentally different host responses in mice compared to H37Rv
Bas C. Mourik,Jurriaan E. M. de Steenwinkel,Gerjo J. de Knegt,Ruth Huizinga,Annelies Verbon,Tom H. M. Ottenhoff,Dick van Soolingen,Pieter J. M. Leenen +7 more
TL;DR: It is suggested that increased virulence of two clinical isolates compared to H37Rv is associated with a fundamentally different systemic immune response, which already can be detected early during infection.
Journal ArticleDOI
iNOS/Arginase-1 expression in the pulmonary tissue over time during Cryptococcus gattii infection.
Patrícia Kellen Martins Oliveira-Brito,Caroline Patini Rezende,Fausto Almeida,Maria Cristina Roque-Barreira,Thiago Aparecido da Silva +4 more
TL;DR: Surprisingly, iNOS knock-out prolonged the survival of infected mice, while their pulmonary fungal burden was higher than that of infected WT mice, and iN OS expression may play a key role in infection progression.
Journal ArticleDOI
One Episode of Self-Resolving Plasmodium yoelii Infection Transiently Exacerbates Chronic Mycobacterium tuberculosis Infection.
TL;DR: One episode of P. yoelii co-infection transiently exacerbated disease severity but had no long-term consequences on disease progression and survival of M. tuberculosis infected mice.
References
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AIM2 recognizes cytosolic dsDNA and forms a caspase-1 activating inflammasome with ASC
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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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