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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Type I IFN Inhibits Alternative Macrophage Activation during Mycobacterium tuberculosis Infection and Leads to Enhanced Protection in the Absence of IFN-γ Signaling
Lúcia Moreira-Teixeira,Lúcia Moreira-Teixeira,Jeremy Sousa,Jeremy Sousa,Finlay W. McNab,Egídio Torrado,Filipa Cardoso,Henrique Machado,Flávia Castro,Vânia Cardoso,Joana Gaifem,Xuemei Wu,Rui Appelberg,António G. Castro,Anne O'Garra,Anne O'Garra,Margarida Saraiva,Margarida Saraiva,Margarida Saraiva +18 more
TL;DR: A novel mechanism by which type I IFN may confer protection against Mycobacterium tuberculosis infection in the absence of IFN-γ signaling is revealed, which supports a model in which suppression of alternative macrophage activation by type IIFN during M. tuberculosis infection contributes to host protection.
Journal ArticleDOI
Principles of inflammasome priming and inhibition: Implications for psychiatric disorders.
TL;DR: There is evidence to support the principle that within primed neuroimmune systems a lowered threshold for NLRP3 activation can cause persistent neuroinflammation or the amplified production of inflammatory cytokines, such as IL-1β and IL-18.
Journal ArticleDOI
Negative regulation of NLRP3 inflammasome signaling.
Shuzhen Chen,Bing Sun +1 more
TL;DR: The developments in the negative regulation of NLRP3 inflammasome that protect host from inflammatory damage are reviewed.
Journal ArticleDOI
Citral alleviates an accelerated and severe lupus nephritis model by inhibiting the activation signal of NLRP3 inflammasome and enhancing Nrf2 activation
Shuk-Man Ka,Jung-Chen Lin,Tsai-Jung Lin,Feng-Cheng Liu,Louis Kuoping Chao,Chen-Lung Ho,Li-Tzu Yeh,Huey-Kang Sytwu,Kuo-Feng Hua,Kuo-Feng Hua,Ann Chen +10 more
TL;DR: Data show that Citral alleviates the mouse ASLN model by inhibition of the activation signal, but not the priming signal, of NLRP3 inflammasome and enhanced activation of Nrf2 antioxidant signaling.
Journal ArticleDOI
In Vivo Expansion of Melanoma-Specific T Cells Using Microneedle Arrays Coated with Immune-Polyelectrolyte Multilayers
TL;DR: MNs coated with PEMs built from tumor vaccine components as a well-defined, modular system for generating tumor-specific immune responses are supported, enabling new approaches that can be explored in combination with checkpoint blockade or other combination cancer therapies.
References
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Erratum: NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals (Nature (2010) 464 (1357-1361))
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