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Infection and Immunity, August 2000, p. 4399-4406, Vol. 68, No. 8
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Central Role of Endogenous Gamma Interferon in Protective Immunity against Blood-Stage Plasmodium chabaudi AS Infection

Zhong Su and Mary M. Stevenson*

Centre for the Study of Host Resistance, Montreal General Hospital Research Institute and McGill University, Montreal, Quebec, Canada

Received 12 January 2000/Returned for modification 25 February 2000/Accepted 1 May 2000

The role of endogenous gamma interferon (IFN-gamma ) in protective immunity against blood-stage Plasmodium chabaudi AS malaria was studied using IFN-gamma gene knockout (GKO) and wild-type (WT) C57BL/6 mice. Following infection with 106 parasitized erythrocytes, GKO mice developed significantly higher parasitemia during acute infection than WT mice and had severe mortality. In infected GKO mice, production of interleukin 12 (IL-12) p70 and tumor necrosis factor alpha in vivo and IL-12 p70 in vitro by splenic macrophages was significantly reduced compared to that in WT mice and the enhanced nitric oxide (NO) production observed in infected WT mice was completely absent. WT and GKO mice had comparable numbers of total nucleated spleen cells and B220+ and Mac-1+ spleen cells both before and after infection. Infected WT mice, however, had significantly more F4/80+, NK1.1+, and F4/80+Ia+ spleen cells than infected GKO mice; male WT had more CD3+ cells than male GKO mice. In comparison with those from WT mice, splenocytes from infected GKO mice had significantly higher proliferation in vitro in response to parasite antigen or concanavalin A stimulation and produced significantly higher levels of IL-10 in response to parasite antigen. Infected WT mice produced more parasite-specific immunoglobulin M (IgM), IgG2a, and IgG3 and less IgG1 than GKO mice. Significant gender differences in both GKO and WT mice in peak parasitemia levels, mortality, phenotypes of spleen cells, and proliferation of and cytokine production by splenocytes in vitro were apparent during infection. These results thus provide unequivocal evidence for the central role of endogenous IFN-gamma in the development of protective immunity against blood-stage P. chabaudi AS.

* 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.

Infection and Immunity, August 2000, p. 4399-4406, Vol. 68, No. 8
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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