The contribution of interleukin-3 (IL-3), a hematopoietic growth factor and immunoregulatory cytokine, to resistance to bloodstage 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, as 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-␥) and CXCL9 (monokine induced by IFN-␥ [MIG]) were found to be significantly reduced in IL-3 KO mice during early stages of infection. In contrast, granulocyte colony-stimulating factor (G-CSF) levels were significantly higher, and the percentage of peripheral blood neutrophils lower, in infected IL-3 KO mice 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-␥, 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.

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.

Interleukin-3 (IL-3), which can be derived from T cells and other sources, is well documented at promoting the in vitro differentiation and proliferation of murine hematopoietic progenitors, yielding multipotential blast cells, mast cells, and mature cells of the myeloid and erythroid lineages. Although IL-3-deficient (knockout [KO]) mice display intact steady-state hematopoiesis, administration of IL-3 to mice and humans can promote hematopoiesis and influence the effector functions of mature hematopoietic cells in vivo. Because of these biological activities of IL-3, the contribution of IL-3 to resistance to blood-stage malaria was investigated by infecting KO mice intraperitoneally with Plasmodium berghei-infected RBCs. We found that KO mice were more susceptible to infection than wild-type (WT) mice, as evidenced by markedly higher peak parasitemia. P. berghei-infected KO mice also had significantly greater anemia and splenomegaly compared to similarly infected WT mice. Our results indicate that IL-3 contributes to resistance to P. berghei infection.