Barakat Farah M, McDonald Vincent, Foster Graham R, Tovey Michael G, Korbel Daniel S
Queen Mary University of London, Institute of Cell and Molecular Science, Centre for Gastroenterology, Barts and the London School of Medicine and Dentistry, 4 Newark Street, London, United Kingdom.
J Infect Dis. 2009 Nov 15;200(10):1548-55. doi: 10.1086/644601.
Type II interferon (IFN), IFN-gamma, is important in innate immunity to the intestinal protozoan parasite Cryptosporidium species, which infects epithelial cells (enterocytes). This investigation is, to our knowledge, the first to characterize the role of type I IFN in innate immunity to this parasite. Pretreatment of human or murine enterocyte cell lines with IFN-alpha/beta inhibited parasite development, and we identified that a key mechanism of cytokine action was to prevent parasite invasion of enterocytes. IFN-alpha/beta was rapidly expressed by infected murine enterocytes and also by bone marrow-derived dendritic cells that were exposed to live parasites. Treatment of neonatal severe combined immunodeficiency mice with anti-IFN-alpha/beta neutralizing antibodies before infection increased oocyst reproduction, as measured at the peak of infection, and parasite numbers in gut epithelium were also increased 2 days after infection. The latter observation correlated with strong intestinal expression of both IFN-alpha and IFN-beta messenger RNA within 24 h after infection. Treatment with anti-IFN-alpha/beta, however, did not reduce early expression of IFN-gamma. These findings identify a novel early innate host response against Cryptosporidium parvum involving IFN-alpha/beta.
II型干扰素（IFN），即γ干扰素，在针对肠道原生动物寄生虫隐孢子虫属的固有免疫中发挥重要作用，该寄生虫可感染上皮细胞（肠上皮细胞）。据我们所知，本研究首次阐述了I型干扰素在针对该寄生虫的固有免疫中的作用。用α/β干扰素预处理人或小鼠肠上皮细胞系可抑制寄生虫发育，并且我们确定细胞因子作用的一个关键机制是阻止寄生虫侵入肠上皮细胞。感染的小鼠肠上皮细胞以及接触活寄生虫的骨髓来源树突状细胞可快速表达α/β干扰素。在感染前用抗α/β干扰素中和抗体处理新生严重联合免疫缺陷小鼠，可增加卵囊繁殖（在感染高峰期测量），并且感染后2天肠道上皮中的寄生虫数量也会增加。后一项观察结果与感染后24小时内肠道中α干扰素和β干扰素信使核糖核酸的强烈表达相关。然而，用抗α/β干扰素处理并未降低γ干扰素的早期表达。这些发现确定了一种针对微小隐孢子虫的新型早期固有宿主反应，该反应涉及α/β干扰素。
