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Induction of an IL7-R+c-Kithi myelolymphoid progenitor critically dependent on IFN-γ signaling during acute malaria

Nature Immunology volume 11, pages 477–485 (2010)Cite this article

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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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Figure 1: Changes in bone marrow hematopoiesis during acute infection with P. chabaudi.
Figure 2: Transient emergence of Lin−IL-7Rα+c-Kithi progenitors during acute infection with P. chabaudi.
Figure 3: Infection-induced Lin−IL-7Rα+c-Kithi cells are bipotent myelolymphoid progenitors.
Figure 4: Infection-induced Lin−IL-7Rα+c-Kithi cells differentiate in vivo into functional myeloid cells.
Figure 5: Contribution of Lin−IL-7Rα+c-Kithi cells to the clearance of malaria-infected erythrocytes in vivo.
Figure 6: Generation of infection-induced Lin−IL-7Rα+c-Kithi cells in Myd88-, Trif-, Tlr9- and Ifngr1-null mutants.
Figure 7: Critical dependence of infection-induced Lin−IL-7Rα+c-Kithi cells on IFN-γ signaling.

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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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  1. Nikolai N Belyaev and Douglas E Brown: These authors contributed equally to the work.

Authors and Affiliations

  1. Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, London, UK

    Nikolai N Belyaev, Douglas E Brown, Ana-Isabel Garcia Diaz & Alexandre J Potocnik

  2. Division of Parasitology, Medical Research Council National Institute for Medical Research, London, UK

    William Jarra & Jean Langhorne

  3. Flow Cytometry Core Facility, Medical Research Council National Institute for Medical Research, London, UK

    Aaron Rae

  4. Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, UK

    Joanne Thompson

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Contributions

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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Correspondence to Alexandre J Potocnik.

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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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