Department of Medical Microbiology and Immunology, Creighton University Medical Center, Omaha, Nebraska, USA.
J Infect Dis. 2010 Jan 1;201(1):160-9. doi: 10.1086/648589.
Expression of B7 costimulatory molecules represents an important compartment of immune response of epithelial cells after microbial infection. We report here that the protozoan parasite Cryptosporidium parvum induced B7-H1 expression in cultured human cholangiocytes. Induced expression of B7-H1 was identified in cells after exposure to infective C. parvum parasite or parasite lysate. Interestingly, the level of microRNA-513 (miR-513) was reduced in cells after exposure to C. parvum, which resulted in a relief of 3' untranslated region-mediated translational suppression of B7-H1. Overexpression of miR-513 through transfection of miR-513 precursor inhibited C. parvum-induced B7-H1 protein expression. Moreover, enhanced apoptotic cell death was identified in activated human T cells after coculture with C. parvum-infected cholangiocytes. The apoptosis of activated T cells was partially blocked by a neutralizing antibody to B7-H1 or transfection of cholangiocytes with miR-513 precursor. These data suggest a role of miR-513 in regulating B7-H1 expression by cholangiocytes in response to C. parvum infection.
B7 共刺激分子的表达是微生物感染后上皮细胞免疫反应的一个重要组成部分。我们在这里报告,原虫寄生虫微小隐孢子虫可诱导培养的人胆管细胞表达 B7-H1。在暴露于感染性微小隐孢子虫寄生虫或寄生虫裂解物后,可在细胞中鉴定出 B7-H1 的诱导表达。有趣的是,暴露于微小隐孢子虫后,细胞中的 microRNA-513(miR-513)水平降低,导致 B7-H1 的 3'非翻译区介导的翻译抑制缓解。通过转染 miR-513 前体过表达 miR-513 可抑制微小隐孢子虫诱导的 B7-H1 蛋白表达。此外,在与微小隐孢子虫感染的胆管细胞共培养后,活化的人 T 细胞中鉴定出增强的细胞凋亡。用 B7-H1 的中和抗体或胆管细胞转染 miR-513 前体可部分阻断活化 T 细胞的凋亡。这些数据表明,miR-513 在调节胆管细胞对微小隐孢子虫感染的 B7-H1 表达中起作用。