Interleukin-3-deficient mice have increased resistance to blood-stage malaria (MPF1P.764)

Abstract

The contribution of interleukin-3 (IL-3), a hematopoietic growth factor and immunoregulatory cytokine, to resistance to blood-stage malaria was investigated by infecting IL-3 deficient (knockout [KO]) mice with Plasmodium berghei NK65. Male IL-3 KO mice, but not female mice, were more resistant to infection than wild-type (WT) mice, evidenced by lower peak parasitemia and prolonged survival. Both male and female IL-3 KO mice had increased splenomegaly and were more anemic than corresponding WT mice. Anemia was compensated for by an increase in bone marrow and splenic erythropoiesis in IL-3 KO mice, as evidenced by higher levels of erythroid progenitors. Plasma levels of gamma interferon (IFN-γ) and CXCL9 (Monokine Induced by IFN-γ; [MIG]) were found to be significantly reduced in IL-3 KO mice during early stages of infection whereas G-CSF levels were significantly greater than in WT counterparts. Overall, our results indicate that IL-3 plays a critical role in suppressing protective immunity to P. berghei NK65 infection and that it is involved in inhibiting the development of splenomegaly, anemia, and erythropoiesis. IL-3 also influences IFN-γ, CXCL9, and G-CSF production in response to infection. The abnormal responses seen in infected IL-3 KO mice may be due to the lack of IL-3 during development, to the lack of IL-3 in the infected mature mice, or to both.

M-MDSC in vitro generation from mouse bone marrow with IL-3 reveals high expression and functional activity of arginase 1

“…IL-3 was also not required for the steady state development of neutrophils. However, after malaria infection, lower percentages of neutrophils were induced as compared to wild-type mice (35). This points towards IL-3 as a growth factor that expands proinflammatory neutrophils only under inflammatory conditions.…”