| First Author | Zhang Y | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 9 | Pages | 4725-35 |
| PubMed ID | 23526822 | Mgi Jnum | J:195524 |
| Mgi Id | MGI:5484717 | Doi | 10.4049/jimmunol.1203024 |
| Citation | Zhang Y, et al. (2013) MyD88 Signaling in CD4 T Cells Promotes IFN-gamma Production and Hematopoietic Progenitor Cell Expansion in Response to Intracellular Bacterial Infection. J Immunol 190(9):4725-35 |
| abstractText | 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-gamma 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-gamma compared with wild-type mice. We next identified CD4 T cells as the primary cells producing IFN-gamma in the bone marrow and demonstrated a nonredundant role for CD4-derived IFN-gamma 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-gamma 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-gamma production is essential for HSPC activation and hematopoietic responses to infection. |
