The Inflammasome Pyrin Contributes to Pertussis Toxin-Induced IL-1β Synthesis, Neutrophil Intravascular Crawling and Autoimmune Encephalomyelitis

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Microbial agents can aggravate inflammatory diseases, such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). An example is pertussis toxin (PTX), which is used to promote EAE by an obscure mechanism. We have reported that PTX triggers an IL-6-mediated signaling cascade that increases the number of leukocytes that patrol the vasculature by crawling on its luminal surface. We show here that PTX, through its ADP-ribosyltransferase activity, induces: 1) TLR4 signaling in myeloid cells, leading to pro-IL-1β synthesis; and 2) a pyrin-dependent inflammasome that cleaves pro-IL-1β into its active form. Then, IL-1β stimulates nearby stromal cells to secrete IL-6. Without pyrin, PTX does not induce neutrophil adhesion to cerebral capillaries and is less effective at inducing EAE in mice with encephalitogenic T lymphocytes. This study identifies the first microbial molecule that activates pyrin, a mechanism by which infections may influence MS and a potential therapeutic target for immune disorders.

Vyšlo v časopise: The Inflammasome Pyrin Contributes to Pertussis Toxin-Induced IL-1β Synthesis, Neutrophil Intravascular Crawling and Autoimmune Encephalomyelitis. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004150
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004150

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