This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Riopel, J.
Right arrow Articles by Stevenson, M. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Riopel, J.
Right arrow Articles by Stevenson, M. M.

 Previous Article  |  Next Article 

Infection and Immunity, January 2001, p. 129-136, Vol. 69, No. 1
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.1.129-136.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Granulocyte-Macrophage Colony-Stimulating Factor-Deficient Mice Have Impaired Resistance to Blood-Stage Malaria

Julie Riopel,1 MiFong Tam,1 Karkada Mohan,1,dagger Michael W. Marino,2 and Mary M. Stevenson1,*

Centre for the Study of Host Resistance, McGill University and The Montreal General Hospital Research Institute, Montreal, Quebec, Canada,1 and Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, New York 100212

Received 28 June 2000/Returned for modification 30 July 2000/Accepted 8 October 2000

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.

* Corresponding author. Mailing address: Montreal General Hospital Research Institute, 1650 Cedar Ave., Montreal, Quebec H3G 1A4, Canada. Phone: (514) 937-6011, ext. 4507. Fax: (514) 934-8332. E-mail: mcev{at}musica.mcgill.ca.

dagger Present address: Department of Pediatrics, IWK Grace Children's Hospital, Halifax, NS B3J 3G9, Canada.

Infection and Immunity, January 2001, p. 129-136, Vol. 69, No. 1
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.1.129-136.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Zarei, S., Schwenter, F., Luy, P., Aurrand-Lions, M., Morel, P., Kopf, M., Dranoff, G., Mach, N. (2009). Role of GM-CSF signaling in cell-based tumor immunization. Blood 113: 6658-6668 [Abstract] [Full Text]  
  • Turcotte, K., Gauthier, S., Malo, D., Tam, M., Stevenson, M. M., Gros, P. (2007). Icsbp1/IRF-8 Is Required for Innate and Adaptive Immune Responses against Intracellular Pathogens. J. Immunol. 179: 2467-2476 [Abstract] [Full Text]  
  • Min-Oo, G., Fortin, A., Pitari, G., Tam, M., Stevenson, M. M., Gros, P. (2007). Complex genetic control of susceptibility to malaria: positional cloning of the Char9 locus. JEM 204: 511-524 [Abstract] [Full Text]  
  • Chen, G.-H., Olszewski, M. A., McDonald, R. A., Wells, J. C., Paine, R. III, Huffnagle, G. B., Toews, G. B. (2007). Role of Granulocyte Macrophage Colony-Stimulating Factor in Host Defense Against Pulmonary Cryptococcus neoformans Infection during Murine Allergic Bronchopulmonary Mycosis. Am. J. Pathol. 170: 1028-1040 [Abstract] [Full Text]  
  • Aiello, F. B., Keller, J. R., Klarmann, K. D., Dranoff, G., Mazzucchelli, R., Durum, S. K. (2007). IL-7 Induces Myelopoiesis and Erythropoiesis. J. Immunol. 178: 1553-1563 [Abstract] [Full Text]  
  • Ballinger, M. N., Paine, R. III, Serezani, C. H. C., Aronoff, D. M., Choi, E. S., Standiford, T. J., Toews, G. B., Moore, B. B. (2006). Role of Granulocyte Macrophage Colony-Stimulating Factor during Gram-Negative Lung Infection with Pseudomonas aeruginosa. Am. J. Respir. Cell Mol. Bio. 34: 766-774 [Abstract] [Full Text]  
  • Angulo, I., Fresno, M. (2002). Cytokines in the Pathogenesis of and Protection against Malaria. CVI 9: 1145-1152 [Full Text]  
  • Fortin, A., Stevenson, M.M., Gros, P. (2002). Susceptibility to malaria as a complex trait: big pressure from a tiny creature. Hum Mol Genet 11: 2469-2478 [Abstract] [Full Text]  
  • Fortin, A., Cardon, L. R., Tam, M., Skamene, E., Stevenson, M. M., Gros, P. (2001). Identification of a malaria new susceptibility locus (Char4) in recombinant congenic strains of mice. Proc. Natl. Acad. Sci. USA 10.1073/pnas.191288998v1 [Abstract] [Full Text]  
  • Fortin, A., Cardon, L. R., Tam, M., Skamene, E., Stevenson, M. M., Gros, P. (2001). Identification of a new malaria susceptibility locus (Char4) in recombinant congenic strains of mice. Proc. Natl. Acad. Sci. USA 98: 10793-10798 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»