Crucial role for T cell-intrinsic IL-18R-MyD88 signaling in cognate immune response to intracellular parasite infection
- Universidade Federal do Rio de Janeiro (UFRJ), Brazil
- The Rockefeller University, United States
- Universidade Federal Fluminense (UFF), Brazil
- Universidade de São Paulo (USP), Brazil
Abstract
MyD88 is the main adaptor molecule for TLR and IL-1R family members. Here, we demonstrated that T-cell intrinsic MyD88 signaling is required for proliferation, protection from apoptosis and expression of activation/memory genes during infection with the intracellular parasite Trypanosoma cruzi, as evidenced by transcriptome and cytometry analyses in mixed bone-marrow (BM) chimeras. The lack of direct IL-18R signaling in T cells, but not of IL-1R, phenocopied the absence of the MyD88 pathway, indicating that IL-18R is a critical MyD88-upstream pathway involved in the establishment of the Th1 response against an in vivo infection, a presently controvert subject. Accordingly, Il18r1-/- mice display lower levels of Th1 cells and are highly susceptible to infection, but can be rescued from mortality by the adoptive transfer of WT CD4+ T cells. Our findings establish the T-cell intrinsic IL-18R/MyD88 pathway as a crucial element for induction of cognate Th1 responses against an important human pathogen.
Data availability
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T cell-intrinsic MyD88 signaling in cognate immune response to intracellular parasite infection: crucial role for IL-18RPublicly available at NCBI Gene Expression Omnibus (accession no. GSE57738).
Article and author information
Author details
Funding
Conselho Nacional de Desenvolvimento Científico e Tecnológico (402932/2012-9)
- Maria Bellio
Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (103.078/2011 and 110.168/2013)
- Maria Bellio
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Urszula Krzych, Walter Reed Army Institute of Research, United States
Ethics
Animal experimentation: Experiments were conducted in strict accordance with guidelines of the Animal Care and Use Committee of the Federal University of Rio de Janeiro (Comitê de Ética do Centro de Ciências da Saúde CEUA-CCS/UFRJ). Procedures and animal protocols were approved by CEUA-CCS/UFRJ license n.: IMPPG022. Every effort was made to minimize suffering.
Version history
- Received: July 30, 2017
- Accepted: September 12, 2017
- Accepted Manuscript published: September 12, 2017 (version 1)
- Version of Record published: September 29, 2017 (version 2)
Copyright
© 2017, Oliveira et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Crucial role for T cell-intrinsic IL-18R-MyD88 signaling in cognate immune response to intracellular parasite infection
eLife 6:e30883.
https://doi.org/10.7554/eLife.30883
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