Okwor Ifeoma, Muleme Helen, Jia Ping, Uzonna Jude E
Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
J Infect Dis. 2009 Aug 1;200(3):361-9. doi: 10.1086/599792.
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.
BALB/c小鼠对刚果锥虫感染高度敏感，而C57BL/6小鼠则相对具有抗性。γ干扰素（IFN-γ）和其他促炎细胞因子的过度产生导致易感小鼠死亡。在此，我们表明，淋巴毒素β缺陷（LTβ(-/-)）小鼠比野生型（WT）小鼠对刚果锥虫感染更具抗性，表现为较低的寄生虫血症水平和更长的存活时间。LTβ(-/-)小鼠抗性增强与促炎细胞因子（即肿瘤坏死因子-α、白细胞介素[IL]-6、IL-12和单核细胞趋化蛋白-1）的血清水平检测不到或较低有关。尽管受感染的LTβ(-/-)小鼠有大量的CD4(+)CD25(+)Foxp3(+)细胞和较高的血清IL-10水平，但这些细胞并非IL-10的主要产生者。用抗IL-10R单克隆抗体处理LTβ(-/-)小鼠消除了它们增强的抗性，而清除CD25(+)细胞进一步增强了受感染的WT和LTβ(-/-)小鼠的抗性。这些结果表明，LTβ在调节小鼠刚果锥虫感染的结果中起关键作用。
