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The generation of immune cells from BM precursors is a carefully regulated process. This is essential to limit the potential for oncogenesis and autoimmunity yet protect against infection. How infection modulates this is unclear. Salmonella can colonize systemic sites including the BM and spleen. This resolving infection has multiple IFN-γ-mediated acute and chronic effects on BM progenitors, and during the first week of infection IFN-γ is produced by myeloid, NK, NKT, CD4(+) T cells, and some lineage-negative cells. After infection, the phenotype of BM progenitors rapidly but reversibly alters, with a peak ∼ 30-fold increase in Sca-1(hi) progenitors and a corresponding loss of Sca-1(lo/int) subsets. Most strikingly, the capacity of donor Sca-1(hi) cells to reconstitute an irradiated host is reduced; the longer donor mice are exposed to infection, and Sca-1(hi) c-kit(int) cells have an increased potential to generate B1a-like cells. Thus, Salmonella can have a prolonged influence on BM progenitor functionality not directly related to bacterial persistence. These results reflect changes observed in leucopoiesis during aging and suggest that BM functionality can be modulated by life-long, periodic exposure to infection. Better understanding of this process could offer novel therapeutic opportunities to modulate BM functionality and promote healthy aging.

Original publication

DOI

10.1002/eji.201344350

Type

Journal article

Journal

European journal of immunology

Publication Date

08/2014

Volume

44

Pages

2318 - 2330

Addresses

MRC Centre for Immune Regulation, Institute for Microbiology and Infection, School of Immunity and Infection, Institute for Biomedical Research, Medical School, University of Birmingham, Edgbaston, Birmingham, UK.

Keywords

CD4-Positive T-Lymphocytes, Bone Marrow Cells, Stem Cells, Animals, Mice, Inbred C57BL, Mice, Knockout, Mice, Salmonella, Salmonella Infections, Animal, Membrane Proteins, Antigens, Ly, Homeostasis, Phenotype, Interferon-gamma