MyD88 signaling in CD4 T cells promotes IFN-? production and hematopoietic progenitor cell expansion in response to intracellular bacterial infection.

ABSTRACT: Hematopoietic stem and progenitor cell (HSPC) phenotype and function can change in response to infectious challenge. These changes can be mediated by cytokines, IFNs, and pathogen-associated molecules, via TLR, and are thought to promote tailored immune responses for particular pathogens. In this study, we investigated the signals that activate HSPCs during ehrlichiosis, a disease characterized by profound hematopoietic dysfunction in both humans and mice. In a mouse model of ehrlichiosis, we observed that infection-induced proliferation of bone marrow HSPCs was dependent on IFN-? signaling and was partially dependent on MyD88. However, MyD88 was not required in HSPCs for their expansion during infection, because similar frequencies of MyD88-deficient and wild-type HSPCs proliferated in mixed bone marrow chimeric mice. MyD88-deficient mice exhibited low serum and bone marrow concentration of IFN-? compared with wild-type mice. We next identified CD4 T cells as the primary cells producing IFN-? in the bone marrow and demonstrated a nonredundant role for CD4-derived IFN-? in increased HSPCs. Using mixed bone marrow chimeric mice, we identified a requirement for MyD88 in CD4 T cells for increased T-bet expression, optimal IFN-? production, and CD4 T cell proliferation. Our data demonstrate an essential role for CD4 T cells in mediating HSPC activation in response to bacterial infection and illustrate a novel role for MyD88 signaling in CD4 T cells in this process. These findings further support the idea that IFN-? production is essential for HSPC activation and hematopoietic responses to infection.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC3633622 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature