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.
journal_name
Elifejournal_title
eLifeauthors
Oliveira AC,Gomes-Neto JF,Barbosa CD,Granato A,Reis BS,Santos BM,Fucs R,Canto FB,Nakaya HI,Nóbrega A,Bellio Mdoi
10.7554/eLife.30883subject
Has Abstractpub_date
2017-09-12 00:00:00issn
2050-084Xpii
30883journal_volume
6pub_type
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