Interferon gamma induces enterocyte resistance against infection by the intracellular pathogen Cryptosporidium parvum
Interferon gamma induces enterocyte resistance against infection by the intracellular pathogen Cryptosporidium parvum
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DOI：
10.1053/gast.2001.20907
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发表时间：
2001-01-01
期刊：
影响因子：
29.4
通讯作者：
McDonald, V
中科院分区：
文献类型：
--
作者：
Pollok, RCG;Farthing, MJG;McDonald, V
背景和目标：干扰素（IFN）-γ在肠道病原体隐孢子虫（Cryptosporidium parvum）感染的免疫控制中起重要作用。我们测试的假设，IFN-γ可能直接抑制这种病原体感染的肠上皮细胞。方法：HT-29、Caco-2和H4人肠上皮细胞系在单层中浸没，并在暴露于C.小的通过Western印迹分析测定细胞系中IFN-γ受体的表达。结果：IFN-γ抑制C. HT-29和Caco-2细胞均被细小病毒感染，但H4细胞未被感染。对IFN-γ的应答与各细胞系中IFN-γ受体的表达有关。IFN-γ的作用通过抑制JAK/STAT信号通路而部分逆转。IFN-γ至少通过2种机制介导其作用：（1）抑制寄生虫入侵和（2）改变细胞内Fe 2+浓度。没有发现色氨酸饥饿或一氧化氮合酶活性的作用。TNF-α和IL-1 β也有抗C。结论：IFN-γ直接诱导肠上皮细胞抵抗小隐孢子虫感染;这一观察结果可能对我们理解粘膜对入侵性病原体的免疫反应具有重要意义。
Background & Aims: Interferon (IFN)-gamma plays an important role in the immunologic control of infection by the protozoan enteropathogen Cryptosporidium parvum. We tested the hypothesis that IFN-gamma may directly inhibit infection of enterocytes by this pathogen. Methods: HT-29, Caco-2, and H4 human enterocyte cell lines were drown in monolayers and incubated with IFN-gamma before exposure with C. parvum. IFN-gamma receptor expression in the cell lines was determined by Western blot analysis. Results: IFN-gamma inhibited C. parvum infection of both HT-29 and Caco-2 cells but not H4 cells. Response to IFN-gamma, was related to the expression of the IFN-gamma receptor in the respective cell lines. The effect of IFN-gamma was partially reversed by inhibition of the JAK/STAT signaling pathway. IFN-gamma mediated its action by at least 2 mechanisms: (1) inhibition of parasite invasion and (2) by modification of intracellular Fe2+ concentration. No role for tryptophan starvation or nitric oxide synthase activity was found. TNF-alpha and IL-1 beta also had anti-C. parvum activity but had no synergistic effect with IFN-gamma, Conclusions: IFN-gamma directly induces enterocyte resistance against C parvum infection; this observation may have important consequences for our understanding of the mucosal immune response to invasive pathogens.