Interferon gamma-dependent alterations in the hematopoietic stem cell pool during infection (87.4)

Abstract

Abstract Infection with Ehrlichia muris induces blood cytopenias and a decrease in bone marrow (BM) cellularity and function. Here we addressed whether infection altered hematopoietic stem cells (HSCs) and progenitor cells. We observed changes in the frequency of BM HSCs by day 8 post-infection; lineage-negative (Lin-), c-Kit-, Sca-1+ progenitor cells were absent, and the Lin- population was composed entirely of c-Kit+, Sca-1+ cells (LSK). In addition, common myeloid progenitors (Lin-, Sca-1-, c-Kit+, CD127-) were diminished and common lymphoid progenitors (LSK, CD127+) were increased. Competitive reconstitution experiments revealed that LSK cells isolated from infected mice gave rise to predominantly B lymphocytes, suggesting that infection favored lymphopoiesis. We next stained Lin- cells for expression of other markers for HSCs (CD150, CD48, and CD244) which revealed that the LSK population were likely true long-term reconstituting HSCs (CD150+, CD48-, CD244-) and multipotential progenitors (CD150-, CD244+, CD48-). We examined several knockout strains in our infection model and found that interferon gamma (IFNg)-deficient mice exhibited reduced CLPs after infection, suggesting that IFNg contributes to alterations in the HSC pool. Current research is aimed at understanding the specific requirement of IFNg in processes that govern HSC self-renewal, differentiation, and mobilization.