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Date of Award
Master of Science (MS)
Department of Biology
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. The results show that endogenous IL-3 significantly alters the susceptibility of BALB/c mice to P. berghei NK65 infection as reflected by measures of survival, anemia, parasitemia, and splenomegaly. 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 male IL-3 KO mice, as evidenced by higher levels of erythroid progenitors. P. berghei NK65 infection was also shown to induce IL-3-dependent changes in plasma cytokine levels: plasma levels of gamma interferon (IFN-γ) and chemokine (C-X-C motif) ligand 9 (CXCL9 or monokine induced by IFN-γ [MIG]) were found to be significantly reduced in male 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 P. berghei NK65-infected male IL-3 KO mice than in WT counterparts. P. berghei NK65 infection induced degranulation of splenic mast cells in both male IL-3 KO and WT mice; however, there was no difference in mast cell numbers between genotypes. 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.
Auclair, Sarah Rebekah, "Interleukin-3-deficient mice have increased resistance to blood-stage malaria" (2014). Masters Theses. 138.