Altered proinflammatory cytokine production and enhanced resistance to Trypanosoma congolense infection in lymphotoxin beta-deficient mice.
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.
Okwor
Ifeoma
I
Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Muleme
Helen
H
Jia
Ping
P
Uzonna
Jude E
JE
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D053308:Lymphotoxin-beta / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018512:Parasitemia; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D014348:Trypanosoma congolense / Q000276:immunology; D014353:Trypanosomiasis, African / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; D053308:Lymphotoxin-beta