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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Mycobacterium tuberculosis evasion of Guanylate Binding Protein-mediated host defense in mice requires the ESX1 secretion system [preprint]
TL;DR: This specific genetic interaction between the murine host and Mycobacteria reveals a novel function for the ESX1 virulence system in the evasion of GBP-mediated immunity.
Journal ArticleDOI
Potentials of Interferons and Hydroxychloroquine for the Prophylaxis and Early Treatment of COVID-19
TL;DR: The reanalysis of the results from two randomized clinical trials (RCTs) has concluded that use of HCQ is beneficial in postexposure prophylaxis and both type I and III IFNs could potentially be beneficial as prophYLaxis and treatment of COVID-19 at the early stage of infection.
Dissertation
Early immune events in Mycobacterium tuberculosis infection and vaccination: protective role for GM-CSF in the primary immune response to Mycobacterium tuberculosis infection and recall responses following vaccination
TL;DR: Overall this thesis demonstrates the importance ofGM-CSF in the primary and recall responses to Mtb infection and identifies ILCs as an early, innate source of GM- CSF.
Dissertation
Mechanism of hepatic inflammation during hepatitis C virus infection
TL;DR: It is shown that interleukin-1 (IL-1) production by intrahepatic macrophages confers liver inflammation through HCV-induced inflammasome signaling, and that Kupffer cells -are the primary cellular source of hepatic IL-1 during HCV infection.
References
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Journal ArticleDOI
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Journal ArticleDOI
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Journal ArticleDOI
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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.
Journal ArticleDOI
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