Inflammasome Sensor NLRP1 Controls Rat Macrophage Susceptibility to

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Inflammasomes are multiprotein complexes that are a major component of the innate immune system. They contain “sensor” proteins that are responsible for detecting various microbial and environmental danger signals and function by activating caspase-1, an enzyme that mediates cleavage and release of the pro-inflammatory cytokines, IL-1β and IL-18. Toxoplasma gondii is a highly successful protozoan parasite capable of infecting a wide range of host species that have variable levels of resistance. Rat strains have been previously shown to vary in their susceptibility to this parasite. We report here that rat macrophages from different inbred strains also vary in sensitivity to Toxoplasma induced lysis. We find that NLRP1, an inflammasome sensor whose only known agonist is anthrax LT, is also activated by Toxoplasma infection. In rats there is a perfect correlation between NLRP1 sequence and macrophage sensitivity to Toxoplasma-induced rapid cell death, inhibition of parasite proliferation, and IL-1β/IL-18 processing. Nlrp1 genes from sensitive rat macrophages can confer sensitivity to this rapid cell death when expressed in Toxoplasma resistant rat macrophages. Our findings suggest Toxoplasma is a new activator of the NLRP1 inflammasome.

Vyšlo v časopise: Inflammasome Sensor NLRP1 Controls Rat Macrophage Susceptibility to. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1003927
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003927

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