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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Caloric Restriction Promotes Immunometabolic Reprogramming Leading to Protection from Tuberculosis.
Carla Palma,Claudia La Rocca,Vincenzo Gigantino,Gabriella Aquino,Giovanni Piccaro,Dario Di Silvestre,Francesca Brambilla,Rossana Rossi,Fabrizia Bonacina,Maria Lepore,Matteo Audano,Nico Mitro,Gerardo Botti,Sara Bruzzaniti,Clorinda Fusco,Claudio Procaccini,Veronica De Rosa,Mario Galgani,Carlo Alviggi,Annibale Alessandro Puca,Fabio Grassi,Tanja Rezzonico-Jost,Giuseppe Danilo Norata,Pierluigi Mauri,Mihai G. Netea,Mihai G. Netea,Paola de Candia,Giuseppe Matarese +27 more
TL;DR: In this article, controlled caloric restriction (CR), not leading to malnutrition, protects susceptible DBA/2 mice against pulmonary Mycobacterium tuberculosis (MTB) infection by reducing bacterial load, lung immunopathology, and generation of foam cells, an MTB reservoir in lung granulomas.
Journal ArticleDOI
Signal transduction analysis of the NLRP3-inflammasome pathway after cellular damage and its paracrine regulation
TL;DR: An Ordinary Differential Equation-based model is presented that investigates the mechanisms of inflammasome activation and regulation in monocytes to predict IL-1β activation kinetics upon a two-step activation by Damage-Associate-Molecular-Particles (DAMP) and extracellular ATP, and investigates mechanisms that control termination of inflammation using two recently identified molecular intervention points in the inflammaome pathway.
Journal ArticleDOI
Mechanisms and targets of the modulatory action of S-nitrosoglutathione (GSNO) on inflammatory cytokines expression
TL;DR: Anti-inflammatory properties of GSNO seem however to prevail, and exploration of the therapeutic potential ofGSNO and analogues appears therefore warranted.
Journal ArticleDOI
Facile Coordination-Precipitation Route to Insoluble Metal Roussin’s Black Salts for NIR-Responsive Release of NO for Anti-Metastasis
Lijuan Chen,Qianjun He,Minyi Lei,Liwei Xiong,Kun Shi,Liwei Tan,Zhaokui Jin,Tianfu Wang,Zhiyong Qian +8 more
TL;DR: This work establishes a new class of NIR-sensitive NO donors, and may spark new inspiration for designing intelligent gas-releasing molecules.
Journal ArticleDOI
Propolis Exerts an Anti-Inflammatory Effect on PMA-Differentiated THP-1 Cells via Inhibition of Purine Nucleoside Phosphorylase.
Abdulmalik M. Alqarni,Kanidta Niwasabutra,Muhamad Sahlan,Hugo Fearnley,James Fearnley,Valerie A. Ferro,David G. Watson +6 more
TL;DR: Results showed that propolis extracts exert an anti-inflammatory effect by inhibition of pro-inflammatory cytokines and by metabolic reprogramming of LPS activity in macrophage cells, suggesting an immunomodulatory effect.
References
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