Apoptosis-Associated Speck–like Protein Containing a Caspase Recruitment Domain Inflammasomes Mediate IL-1β Response and Host Resistance to Trypanosoma cruzi Infection

摘要: The innate immune response to Trypanosoma cruzi infection comprises several pattern recognition receptors (PRRs), including TLR-2, -4, -7, and -9, as well the cytosolic receptor Nod1. However, there are additional PRRs that account for host responses T. cruzi. In this context, nucleotide-binding oligomerization domain-like (NLRs) activate inflammasomes candidate deserve renewed investigation. Following pathogen infection, NLRs form large molecular platforms, termed inflammasomes, which caspase-1 induce production of active IL-1β IL-18. study, we evaluated involvement in demonstrated apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) NLR family, pyrin domain-containing 3 (NLRP3), but not 4 or 6, required triggering activation secretion IL-1β. mechanism by mediates ASC/NLRP3 pathway involves K⁺ efflux, lysosomal acidification, reactive oxygen species generation, damage. We also demonstrate despite normal IFN-γ heart, ASC⁻/⁻ caspase-1⁻/⁻ infected mice exhibit higher incidence mortality, cardiac parasitism, heart inflammation. These data suggest ASC critical determinants resistance with