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Open AccessJournal ArticleDOI

Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome-dependent processing of IL-1β.

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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.

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Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: Immunity interruptus

TL;DR: The current understanding of pulmonary T cell responses following M. tuberculosis infection is reviewed and it is becoming clear that T cell dysfunction impairs host resistance.
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ESAT-6-dependent cytosolic pattern recognition drives noncognate tuberculosis control in vivo.

TL;DR: It is reported that noncognate IFN-γ production by Mtb antigen-independent memory CD8+ T cells and NK cells is protective during Mtb infection and the mechanistic regulation of IFNs production by these cells in vivo is evaluated.
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More than just protein building blocks: how amino acids and related metabolic pathways fuel macrophage polarization

TL;DR: In this paper, the authors highlight recent advances in macrophage biology and immunometabolism with a specific focus on amino acid metabolism and their related metabolic pathways: urea cycle (arginine), TCA cycle and OXPHOS (glutamine) as well as the one carbon metabolism (serine, glycine).
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NLRP3 Activation Was Regulated by DNA Methylation Modification during Mycobacterium tuberculosis Infection.

TL;DR: It is shown that NLRP3 activation was regulated by DNA methylation modification and provided a new insight into the relationship between host and pathogens.
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NOSH-NBP, a Novel Nitric Oxide and Hydrogen Sulfide- Releasing Hybrid, Attenuates Ischemic Stroke-Induced Neuroinflammatory Injury by Modulating Microglia Polarization.

TL;DR: Findings indicated that NOSH-NBP is a potential therapeutic agent that preferentially promotes microglial/macrophage M1–M2 switch in ischemic stroke.
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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AIM2 recognizes cytosolic dsDNA and forms a caspase-1 activating inflammasome with ASC

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))

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.
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