eLife (Sep 2017)

Crucial role for T cell-intrinsic IL-18R-MyD88 signaling in cognate immune response to intracellular parasite infection

  • Ana-Carolina Oliveira,
  • João Francisco Gomes-Neto,
  • Carlos-Henrique Dantas Barbosa,
  • Alessandra Granato,
  • Bernardo S Reis,
  • Bruno Maia Santos,
  • Rita Fucs,
  • Fábio B Canto,
  • Helder I Nakaya,
  • Alberto Nóbrega,
  • Maria Bellio

DOI
https://doi.org/10.7554/eLife.30883
Journal volume & issue
Vol. 6

Abstract

Read online

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.

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