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
Citations
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Decoding Early Immune Events in Non-human Primates Infected with Mycobacterium tuberculosis
TL;DR: A novel genomic barcoding approach is developed to add to the in vivo toolbox permitting single-bacterial tracing to probe early events in a variety of infection contexts and reiterates the importance of appreciating the influence that early infection and single lesion dynamics contributes to host outcome.
Dissertation
Clinical strains of mycobacterium tuberculosis induce strain-specific patterns of cytokine production, gene expression and pathway changes in pulmonary alveolar epithelial cells.
TL;DR: Cytokine/chemokine production was induced by the Beijing and Unique strains at alltime intervals, suggesting a higher virulence of these strains compared to other strain families, and the F15/LAM4/KZN strain induced high protective cytokine production, suggest a lower virulence for this strain.
Journal ArticleDOI
Independent and inter-dependent immunoregulatory effects of NCF1 and NOS2 in experimental autoimmune encephalomyelitis
TL;DR: These studies show that NCF1 and NOS2 interact to regulate peptide-induced EAE, as compared with Nos2-deficient mice.
Journal ArticleDOI
C Proteins: Controllers of Orderly Paramyxovirus Replication and of the Innate Immune Response
TL;DR: Multiple independent systems to counteract host defenses may ensure efficient immune evasion and facilitate virus adaptation to new hosts and tissue environments.
Posted ContentDOI
Host-pathogen genetic interactions underlie tuberculosis susceptibility
Clare M. Smith,Clare M. Smith,Richard Baker,Megan K. Proulx,Bibhuti B. Mishra,Bibhuti B. Mishra,Jarukit E. Long,Sae Woong Park,Ha-Na Lee,Michael C. Kiritsy,Michelle M. Bellerose,Andrew J. Olive,Kenan C. Murphy,K. G. Papavinasasundaram,Frederick J. Boehm,Charlotte J. Reames,Rachel K. Meade,Brea K. Hampton,Colton L. Linnertz,Ginger D. Shaw,Pablo Hock,Timothy A. Bell,Sabine Ehrt,Dirk Schnappinger,Fernando Pardo-Manuel de Villena,Martin T. Ferris,Thomas R. Ioerger,Christopher M. Sassetti +27 more
TL;DR: In this article, the authors leveraged the genetically diverse Collaborative Cross (CC) mouse panel in conjunction with a library of Mtb mutants to associate bacterial genetic requirements with host genetics and immunity.
References
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