Pollok R C, Farthing M J, Bajaj-Elliott M, Sanderson I R, McDonald V
Digestive Diseases Research Centre, St. Bartholomew's and The Royal London School of Medicine and Dentistry, London, England.
Gastroenterology. 2001 Jan;120(1):99-107. doi: 10.1053/gast.2001.20907.
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.
HT-29, Caco-2, and H4 human enterocyte cell lines were grown 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.
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 Fe(2+) concentration. No role for tryptophan starvation or nitric oxide synthase activity was found. TNF-alpha and IL-1beta also had anti-C. parvum activity but had no synergistic effect with IFN-gamma.
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.
干扰素-γ（IFN-γ）在原生动物肠道病原体微小隐孢子虫感染的免疫控制中发挥重要作用。我们检验了IFN-γ可能直接抑制该病原体对肠上皮细胞感染的假说。
将HT-29、Caco-2和H4人肠上皮细胞系培养成单层，在暴露于微小隐孢子虫之前用IFN-γ孵育。通过蛋白质印迹分析确定细胞系中IFN-γ受体的表达。
IFN-γ抑制了HT-29和Caco-2细胞的微小隐孢子虫感染，但未抑制H4细胞。对IFN-γ的反应与相应细胞系中IFN-γ受体的表达有关。JAK/STAT信号通路的抑制可部分逆转IFN-γ的作用。IFN-γ通过至少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。未发现色氨酸饥饿或一氧化氮合酶活性起作用。肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）也具有抗微小隐孢子虫活性，但与IFN-γ无协同作用。
IFN-γ直接诱导肠上皮细胞对微小隐孢子虫感染产生抗性；这一观察结果可能对我们理解对侵袭性病原体的黏膜免疫反应具有重要意义。
