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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Tolerating the Unwelcome Guest; How the Host Withstands Persistent Mycobacterium tuberculosis
TL;DR: This work examines general strategies used by macrophages and T cells to promote tolerance in the context of tuberculosis, and focuses on pathways, such as regulation of inflammasome activation, that are emerging as common mediators of tolerance.
Journal ArticleDOI
Dendritic cell-derived nitric oxide inhibits the differentiation of effector dendritic cells
Chuanping Si,Ruihua Zhang,Tianshu Wu,Geming Lu,Yuan Hu,Hui Zhang,Feihong Xu,Peter Wei,Kang Chen,Hua Tang,Garabet Yeretssian,Huabao Xiong +11 more
TL;DR: It is shown that DC-derived nitric oxide (NO) controls the balance of effector and regulatory DC differentiation and offers the basis of therapeutic targeting of iNOS in DCs to treat autoimmune and inflammatory diseases.
Journal ArticleDOI
The intrinsic and extrinsic elements regulating inflammation.
TL;DR: Inflammation seems to be a smart process that acts like two edges of a sword, meaning that it has both protective and deleterious consequences, which will help the future understanding and therapy for various diseases.
Journal ArticleDOI
An Inflammatory Story: Antibodies in Tuberculosis Comorbidities.
TL;DR: It is proposed that inflammatory antibody profiles, which are a marker of active TB, may be an important biomarker for detection of TB disease progression within comorbid individuals.
Journal ArticleDOI
Striking the Right Balance Determines TB or Not TB
Somdeb BoseDasgupta,Jean Pieters +1 more
TL;DR: Several of the strategies that M. tuberculosis employs to circumvent host immunity are discussed, as well as some of the mechanisms that the host uses to counter such subversive strategies.
References
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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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