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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Regulation of the NLRP3 Inflammasome by Posttranslational Modifications
TL;DR: The posttranslational modifications that regulate NLRP3 inflammasome components, including ubiquitination, phosphorylation, and other forms of posttranslated modifications are described.
Journal Article
Results of a Phase 2 Efficacy and Safety Study with SB204, an Investigational Topical Nitric Oxide-releasing Drug for the Treatment of Acne Vulgaris.
Hilary E. Baldwin,Daisy Blanco,Charles McKeever,Nelly Paz,Ynca Nina Vasquez,John Quiring,Carolyn Enloe,Emily De Leon,Nathan Stasko +8 more
TL;DR: Both concentrations of topical SB204 were safe and well-tolerated and when compared to vehicle, both SB204 1% and SB204 4% significantly decreased the percentage of noninflammatory lesions and SB 204 4% also significantly decreasedThe percentage of inflammatory lesions in subjects with acne vulgaris treated for 12 weeks.
Journal ArticleDOI
Type 2 Diabetes Mellitus: A Metabolic Autoinflammatory Disease
TL;DR: The importance of inflammasome activation in the central and peripheral mechanisms underlying a common, multifactorial, lifestyle-related, and polygenetic disease (type 2 diabetes mellitus) is reviewed, and the notion that this health challenge should now be recognized to have an autoinflammatory cause is conceptualized.
Journal ArticleDOI
Evaluation of IL-1 Blockade as an Adjunct to Linezolid Therapy for Tuberculosis in Mice and Macaques
Caylin G. Winchell,Bibhuti B. Mishra,Bibhuti B. Mishra,Jia Yao Phuah,Mohd Saqib,Samantha J. Nelson,Pauline Maiello,Chelsea M Causgrove,Cassaundra Ameel,Brianne Stein,H. Jacob Borish,Alexander G. White,Edwin Klein,Matthew D. Zimmerman,Véronique Dartois,Philana Ling Lin,Christopher M. Sassetti,JoAnne L. Flynn +17 more
TL;DR: The data support that inhibition of IL-1 in combination with LZD has potential to be an effective HDT for TB and the need for further research in this area.
Journal ArticleDOI
TNF-α and CD8+ T cells mediate the beneficial effects of nitric oxide synthase-2 deficiency in pulmonary paracoccidioidomycosis.
Simone Bernardino,Adriana Pina,Maíra Felonato,Tânia Alves da Costa,Eliseu Frank de Araújo,Claudia Feriotti,Silvia B. Bazan,Alexandre C. Keller,Katia R. M. Leite,Vera Lúcia Garcia Calich +9 more
TL;DR: It was demonstrated that NO plays a deleterious role in pulmonary paracoccidioidomycosis due to its suppressive action on TNF-α production, T cell immunity and organization of lesions resulting in precocious mortality of mice and revealed that uncontrolled fungal growth can be overcome by an efficient immune response.
References
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