Abstract
Although the relationship between hematopoietic stem cells and progenitor populations has been investigated extensively under steady-state conditions, the dynamic response of the hematopoietic compartment during acute infection is largely unknown. Here we show that after infection of mice with Plasmodium chabaudi, a c-Kithi progenitor subset positive for interleukin 7 receptor-α (IL-7Rα) emerged that had both lymphoid and myeloid potential in vitro. After being transferred into uninfected alymphoid or malaria-infected hosts, IL-7Rα+c-Kithi progenitors generated mainly myeloid cells that contributed to the clearance of infected erythrocytes in infected hosts. The generation of these infection-induced progenitors was critically dependent on interferon-γ (IFN-γ) signaling in hematopoietic progenitors. Thus, IFN-γ is a key modulator of hematopoiesis and innate and adaptive immunity during acute malaria infection.
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Acknowledgements
Supported by the European Commission Framework Programme 6 Network of Excellence (BioMalPar LSHP-CT-2004-503578 to J.L. and MUGEN LSHG-CT-2005-005203 to A.J.P.) and the Medical Research Council UK (U117584248 to J.L. and U117569359 to A.J.P.).
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N.N.B. and D.E.B. did experiments, analyzed data and contributed to the writing of the manuscript; A.-I.G.D. and W.J. did experiments and provided advice; A.R. did the cell sorting; J.T. provided reagents; and J.L. and A.J.P. designed the experiments and wrote the manuscript.
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Belyaev, N., Brown, D., Diaz, AI. et al. Induction of an IL7-R+c-Kithi myelolymphoid progenitor critically dependent on IFN-γ signaling during acute malaria. Nat Immunol 11, 477–485 (2010). https://doi.org/10.1038/ni.1869
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DOI: https://doi.org/10.1038/ni.1869
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