| First Author | Silva GK | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 6 | Pages | 3373-83 |
| PubMed ID | 23966627 | Mgi Jnum | J:205856 |
| Mgi Id | MGI:5546541 | Doi | 10.4049/jimmunol.1203293 |
| Citation | Silva GK, et al. (2013) Apoptosis-associated speck-like protein containing a caspase recruitment domain inflammasomes mediate IL-1beta response and host resistance to Trypanosoma cruzi infection. J Immunol 191(6):3373-83 |
| abstractText | The innate immune response to Trypanosoma cruzi infection comprises several pattern recognition receptors (PRRs), including TLR-2, -4, -7, and -9, as well as the cytosolic receptor Nod1. However, there are additional PRRs that account for the host immune responses to T. cruzi. In this context, the nucleotide-binding oligomerization domain-like receptors (NLRs) that activate the inflammasomes are candidate receptors that deserve renewed investigation. Following pathogen infection, NLRs form large molecular platforms, termed inflammasomes, which activate caspase-1 and induce the production of active IL-1beta and IL-18. In this study, we evaluated the involvement of inflammasomes in T. cruzi infection and demonstrated that apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) inflammasomes, including NLR family, pyrin domain-containing 3 (NLRP3), but not NLR family, caspase recruitment domain-containing 4 or NLR family, pyrin domain-containing 6, are required for triggering the activation of caspase-1 and the secretion of IL-1beta. The mechanism by which T. cruzi mediates the activation of the ASC/NLRP3 pathway involves K(+) efflux, lysosomal acidification, reactive oxygen species generation, and lysosomal damage. We also demonstrate that despite normal IFN-gamma production in the heart, ASC(-)/(-) and caspase-1(-)/(-) infected mice exhibit a higher incidence of mortality, cardiac parasitism, and heart inflammation. These data suggest that ASC inflammasomes are critical determinants of host resistance to infection with T. cruzi. |
