Guo X, Stroup S E, Houpt E R
Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA.
Mucosal Immunol. 2008 Mar;1(2):139-46. doi: 10.1038/mi.2007.18. Epub 2008 Jan 9.
The mechanisms whereby certain mouse strains develop persistent intestinal infection with Entamoeba histolytica remain unclear. In this work, we characterized the kinetic pattern of cytokine responses during the course of natural infection in CBA mice and showed that intracecal amebic infection led to a rapid and sustained upregulation of Th2 (IL-4, IL-5, IL-13) and Th17 cytokine responses while Th1 cytokines, IL-12p35 and interferon (IFN)-gamma, were suppressed. Depletion of IL-4 cleared infection by 14 days post-challenge, and this clearance correlated with and was mediated by IFN-gamma. The protective role for IFN-gamma was not strain-specific, as 129 background IFN-gammaR knockout mice exhibited a higher infection rate than their wild-type littermates. These studies indicate that IL-4 plays a critical pathogenic role in the persistence of E. histolytica infection through suppression of protective IFN-gamma and provide a possible explanation for why certain humans spontaneously clear amebiasis while others progress to invasive disease.
某些小鼠品系发生溶组织内阿米巴持续性肠道感染的机制仍不清楚。在这项研究中，我们对CBA小鼠自然感染过程中细胞因子反应的动力学模式进行了表征，结果显示盲肠内阿米巴感染导致Th2（IL-4、IL-5、IL-13）和Th17细胞因子反应迅速且持续上调，而Th1细胞因子IL-12p35和干扰素（IFN）-γ受到抑制。IL-4缺失使攻毒后14天的感染得以清除，这种清除与IFN-γ相关且由其介导。IFN-γ的保护作用并非品系特异性，因为129背景的IFN-γR基因敲除小鼠比其野生型同窝小鼠表现出更高的感染率。这些研究表明，IL-4通过抑制保护性IFN-γ在溶组织内阿米巴感染的持续存在中发挥关键致病作用，并为为什么某些人能自发清除阿米巴病而另一些人会进展为侵袭性疾病提供了一种可能的解释。
