Granulocyte-macrophage colony-stimulating factor-deficient mice have impaired resistance to blood-stage malaria Journal Article


Authors: Riopel, J.; Tam, M.; Mohan, K.; Marino, M. W.; Stevenson, M. M.
Article Title: Granulocyte-macrophage colony-stimulating factor-deficient mice have impaired resistance to blood-stage malaria
Abstract: The contribution of granulocyte-macrophage colony-stimulating factor (GM-CSF), a hematopoietic and immunoregulatory cytokine, to resistance to blood-stage malaria was investigated by infecting GM-CSF-deficient (knockout [KO]) mice with Plasmodium chabaudi AS. KO mice were more susceptible to infection than wild-type (WT) mice, as evidenced by higher peak parasitemia, recurrent recrudescent parasitemia, and high mortality. P. chabaudi AS-infected KO mice had impaired splenomegaly and lower leukocytosis but equivalent levels of anemia compared to infected WT mice. Both bone marrow and splenic erythropoiesis were normal in infected KO mice. However, granulocyte-macrophage colony formation was significantly decreased in these tissues of uninfected and infected KO mice, and the numbers of macrophages in the spleen and peritoneal cavity were significantly lower than in infected WT mice Serum levels of gamma interferon (IFN-gamma) were found to be significantly higher in uninfected KO mice, and the level of this cytokine was not increased during infection. In contrast, IFN-gamma levels were significantly above normal levels in infected WT mice. During infection, tumor necrosis factor alpha (TNF-alpha) levels were significantly increased in KO mice and were significantly higher than TNF-alpha levels in infected WT mice. Our results indicate that GM-CSF contributes to resistance to P. chabaudi AS infection and that it is involved in the development of splenomegaly, leukocytosis, and granulocyte-macrophage hematopoiesis. GM-CSF may also regulate IFN-gamma and TNF-alpha production and activity in response to infection. The abnormal responses seen in infected KO mice may be due to the lack of GM-CSF during development, to the lack of GM-CSF in the infected mature mice, or to both.
Keywords: tumor-necrosis-factor; factor-alpha; gm-csf; listeria-monocytogenes; human monocytes; plasmodium-yoelii malaria; murine malaria; differential induction; susceptible mice; splenic control
Journal Title: Infection and Immunity
Volume: 69
Issue: 1
ISSN: 0019-9567
Publisher: American Society for Microbiology  
Date Published: 2001-01-01
Start Page: 129
End Page: 136
Language: English
ACCESSION: WOS:000165943500017
DOI: 10.1128/iai.69.1.129-136.2001
PROVIDER: wos
PMCID: PMC97864
PUBMED: 11119498
Notes: Article -- Source: Wos
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  1. Michael W. Marino
    35 Marino