Author | Silva, Grace Kelly | |
Author | Costa, Renata Sesti | |
Author | Silveira, Tatiana Nunes | |
Author | Horta, Catarina Veltrini | |
Author | Guedes, Paulo Marcos da Matta | |
Author | Andrade, Warrison Athanásio | |
Author | Niz, Mariana de | |
Author | Zamboni, Dario Simões | |
Author | Silva, João Santana | |
Access date | 2023-07-05T17:07:22Z | |
Available date | 2023-07-05T17:07:22Z | |
Document date | 2013 | |
Citation | SILVA, Grace Kelly et al. Apoptosis-Associated Speck–like Protein Containing a Caspase Recruitment Domain Inflammasomes Mediate IL-1β Response and Host Resistance to Trypanosoma cruzi Infection. The Journal of Immunology, v. 191, n. 6, p. 3373–3383, 2013. | en_US |
ISSN | 0022-1767 | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/59430 | |
Language | eng | en_US |
Publisher | American Association of Immunologists | en_US |
Rights | restricted access | en_US |
Title | Apoptosis-Associated Speck-like Protein Containing a Caspase Recruitment Domain Inflammasomes Mediate IL-1 beta Response and Host Resistance to Trypanosoma cruzi Infection | en_US |
Type | Article | en_US |
DOI | 10.4049/jimmunol.1203293 | |
Abstract | 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-1 beta 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-1 beta. 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. | en_US |
Affilliation | Department of Biochemistry and Immunology. Ribeirão Preto Medical School. University of São Paulo. Ribeirão Preto, SP, Brazil / Department of Cellular Biology. Ribeirão Preto Medical School. University of São Paulo. Ribeirão Preto, SP, Brazil. | en_US |
Affilliation | Department of Biochemistry and Immunology. Ribeirão Preto Medical School. University of São Paulo. Ribeirão Preto, SP, Brazil. | en_US |
Affilliation | Department of Cellular Biology. Ribeirão Preto Medical School. University of São Paulo. Ribeirão Preto, SP, Brazil. | en_US |
Affilliation | Department of Cellular Biology. Ribeirão Preto Medical School. University of São Paulo. Ribeirão Preto, SP, Brazil. | en_US |
Affilliation | Departamento de Microbiologia e Parasitologia. Universidade Federal do Rio Grande do Norte. Natal, RN, Brazil. | en_US |
Affilliation | Division of Infectious Diseases and Immunology. Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA / Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil / Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Institute of Cell Biology. University of Bern. Bern. Switzerland/Barcelona Center for International Health Research. Barcelona, Spain. | en_US |
Affilliation | Department of Cellular Biology. Ribeirão Preto Medical School. University of São Paulo. Ribeirão Preto, São Paulo, Brazil. | en_US |
Affilliation | Department of Cellular Biology. Ribeirão Preto Medical School. University of São Paulo. Ribeirão Preto, SP, Brazil. | en_US |
Embargo date | 2030-12-31 | |