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

• Published in: eLife Vol. 6
• Main Authors: Oliveira, Ana-Carolina, Gomes-Neto, João Francisco, Barbosa, Carlos-Henrique Dantas, Granato, Alessandra, Reis, Bernardo S, Santos, Bruno Maia, Fucs, Rita, Canto, Fábio B, Nakaya, Helder I, Nóbrega, Alberto, Bellio, Maria
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 12.09.2017; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Adoptive Transfer; Analysis; Animals; Apoptosis; Bone marrow; CD4 antigen; Chagas Disease - immunology; Chagas Disease - therapy; Chimeras; Cloning; Cytometry; Disease Models, Animal; Disease susceptibility; Displays (Marketing); Flow Cytometry; Gene expression; Gene Expression Profiling; Genes; Health aspects; Immune response; Immunology and Inflammation; Infection; Infections; Interleukin 1; Interleukin 1 receptors; Interleukin-18 Receptor alpha Subunit - metabolism; Intracellular; Intracellular signalling; Lymphocytes; Lymphocytes T; Mice, Inbred C57BL; Mice, Knockout; MyD88; MyD88 protein; Myeloid Differentiation Factor 88 - metabolism; Parasitic diseases; Pathogens; Signal Transduction; Survival Analysis; T cells; Th1; Th1 Cells - immunology; Th1 Cells - parasitology; Transcription activation; Trypanosoma cruzi; Trypanosoma cruzi - immunology; Canada; mouse; Th1; MyD88; immunology; Trypanosoma cruzi
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.30883

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 , 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 infection, a presently controvert subject. Accordingly, 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.