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Interleukin-17-Mediated Control of Parasitemia in Experimental Trypanosoma congolense Infection in Mice

Author:
Mou, Zhirong, Jia, Ping, Kuriakose, Shiby, Khadem, Forough, Uzonna, Jude E.
Source:
Infection and immunity 2010 v.78 no.12 pp. 5271-5279
ISSN:
0019-9567
Subject:
African trypanosomiasis, Trypanosoma congolense, alanine transaminase, aspartate transaminase, blood serum, hepatocytes, inflammation, interleukin-10, mice, monoclonal antibodies, neutralization, nitric oxide, parasitemia, parasites, pathogenesis, spleen
Abstract:
BALB/c mice are highly susceptible to experimental Trypanosoma congolense infections, whereas C57BL/6 mice are relatively resistant. Infected highly susceptible BALB/c mice die of systemic inflammatory response syndrome. Because interleukin-17 (IL-17) and Th17 cells regulate inflammatory responses, we investigated their role in the pathogenesis of experimental African trypanosomiasis in mice. We show that the production of IL-17 by spleen and liver cells and the serum IL-17 level increased after T. congolense infection in mice. Interestingly, infected highly susceptible BALB/c mice produced more IL-17 and had more Th17 cells than infected relatively resistant C57BL/6 mice. Paradoxically, neutralization of IL-17 with anti-IL-17 monoclonal antibody in vivo induced higher parasitemia in both the susceptible and the relatively resistant mice. Interestingly, anti-IL-17 antibody-treated mice had higher serum levels of alanine aminotransferase and aspartate aminotransferase, and the production of IL-10 and nitric oxide by liver cells was markedly decreased. Moreover, recombinant IL-17-treated mice exhibited significantly faster parasite control and lower peak parasitemia compared to control mice. Collectively, these results suggest that the IL-17/Th17 axis plays a protective role in murine experimental African trypanosomiasis.
Agid:
287886