Altered proinflammatory cytokine production and enhanced resistance to Trypanosoma congolense infection in lymphotoxin beta-deficient mice.

Abstract

BALB/c mice are highly susceptible to Trypanosoma congolense infection, whereas C57BL/6 mice are relatively resistant. Overproduction of interferon-gamma (IFN-gamma) and other proinflammatory cytokines contribute to death in susceptible mice. Here, we show that lymphotoxin beta-deficient (LTbeta(-/-)) mice are more resistant than wild-type (WT) mice to T. congolense infection, as shown by a lower parasitemia level and a longer survival duration. The enhanced resistance of LTbeta(-/-) mice was associated with undetectable or low serum levels of proinflammatory cytokines (i.e., tumor necrosis factor-alpha, interleukin [IL]-6, IL-12, and monocyte chemotactic protein-1). Although infected LTbeta(-/-) mice had high numbers of CD4(+)CD25(+)Foxp3(+) cells and high serum IL-10 levels, these cells were not the major producers of IL-10. Treatment of LTbeta(-/-) mice with anti-IL-10R monoclonal antibody abolished their enhanced resistance, whereas depletion of CD25(+) cells further enhanced resistance among infected WT and LTbeta(-/-) mice. These results suggest that LTbeta plays critical role in regulating the outcome of T. congolense infection in mice.

• Authors: Ifeoma Okwor, Helen Muleme, Ping Jia, Jude E Uzonna
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 200 Issue 3 Pg. 361-9 (Aug 01 2009) ISSN: 0022-1899 [Print] United States
• PMID: 19563258 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Lymphotoxin-beta

Topics

• Animals
• Cytokines (genetics, metabolism)
• Female
• Gene Deletion
• Gene Expression
• Genetic Predisposition to Disease
• Lymphotoxin-beta (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Parasitemia
• Signal Transduction
• Specific Pathogen-Free Organisms
• Trypanosoma congolense (immunology)
• Trypanosomiasis, African (genetics, immunology)