Induction of an IL7-R(+)c-Kit(hi) myelolymphoid progenitor critically dependent on IFN-gamma signaling during acute malaria.
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-Kit(hi) progenitor subset positive for interleukin 7 receptor-alpha (IL-7Ralpha) emerged that had both lymphoid and myeloid potential in vitro. After being transferred into uninfected alymphoid or malaria-infected hosts, IL-7Ralpha(+)c-Kit(hi) 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-gamma (IFN-gamma) signaling in hematopoietic progenitors. Thus, IFN-gamma is a key modulator of hematopoiesis and innate and adaptive immunity during acute malaria infection.
Belyaev
Nikolai N
NN
Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, London, UK.
Brown
Douglas E
DE
Diaz
Ana-Isabel Garcia
AI
Rae
Aaron
A
Jarra
William
W
Thompson
Joanne
J
Langhorne
Jean
J
Potocnik
Alexandre J
AJ
D056704:Adaptive Immunity; D000818:Animals; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology*; D008288:Malaria / Q000276:immunology*; D051379:Mice; D023461:Myeloid Progenitor Cells / Q000276:immunology*; D016788:Plasmodium chabaudi; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology*; D020395:Receptors, Interleukin-7 / Q000276:immunology*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology
D020395:Receptors, Interleukin-7; D007371:Interferon-gamma; D019009:Proto-Oncogene Proteins c-kit