title: Interleukin-3-deficient mice have increased resistance to blood-stage malaria.
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, 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-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. 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-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.
authors.affiliation: Department of Biology, James Madison University, Harrisonburg, Virginia, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Auclair
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Roth
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Saunders
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Ogborn
authors.forename: Abdalla A
authors.initials: AA
authors.lastname: Sheikh
authors.forename: Julianne
authors.initials: J
authors.lastname: Naples
authors.forename: Anna Marie P
authors.initials: AM
authors.lastname: Young
authors.forename: Dorottya K
authors.initials: DK
authors.lastname: Boisen
authors.forename: Amelia T
authors.initials: AT
authors.lastname: Tavangar
authors.forename: Jane E
authors.initials: JE
authors.lastname: Welch
authors.forename: Chris S
authors.initials: CS
authors.lastname: Lantz
mesh_terms: D000740:Anemia / Q000097:blood / Q000276:immunology / Q000378:metabolism; D000818:Animals; D054370:Chemokine CXCL9 / Q000097:blood; D004920:Erythropoiesis / Q000276:immunology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D007377:Interleukin-3 / Q000172:deficiency* / Q000276:immunology* / Q000378:metabolism; D008288:Malaria / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism; D010962:Plasmodium berghei / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism
chemical_list: D054370:Chemokine CXCL9; C485969:Cxcl9 protein, mouse; D007377:Interleukin-3; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma