National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); Key Laboratory of Parasite and Vector Biology, National Health Commission of People's Republic of China; WHO Collaborating Center for Tropical Diseases, Shanghai, China.
The School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PLoS Negl Trop Dis. 2021 Nov 24;15(11):e0009949. doi: 10.1371/journal.pntd.0009949. eCollection 2021 Nov.
Cryptosporidium is a life-threating protozoan parasite belonging to the phylum Apicomplexa, which mainly causes gastroenteritis in a variety of vertebrate hosts. Currently, there is a re-emergence of Cryptosporidium infection; however, no fully effective drug or vaccine is available to treat Cryptosporidiosis. In the present study, to better understand the detailed interaction between the host and Cryptosporidium parvum, a large-scale label-free proteomics study was conducted to characterize the changes to the proteome induced by C. parvum infection. Among 4406 proteins identified, 121 proteins were identified as differentially abundant (> 1.5-fold cutoff, P < 0.05) in C. parvum infected HCT-8 cells compared with uninfected cells. Among them, 67 proteins were upregulated, and 54 proteins were downregulated at 36 h post infection. Analysis of the differentially abundant proteins revealed an interferon-centered immune response of the host cells against C. parvum infection and extensive inhibition of metabolism-related enzymes in the host cells caused by infection. Several proteins were further verified using quantitative real-time reverse transcription polymerase chain reaction and western blotting. This systematic analysis of the proteomics of C. parvum-infected HCT-8 cells identified a wide range of functional proteins that participate in host anti-parasite immunity or act as potential targets during infection, providing new insights into the molecular mechanism of C. parvum infection.
隐孢子虫是一种属于顶复门的有生命威胁的原生动物寄生虫，主要在各种脊椎动物宿主中引起肠胃炎。目前，隐孢子虫感染再次出现；然而，目前尚无完全有效的药物或疫苗可用于治疗隐孢子虫病。在本研究中，为了更好地了解宿主与微小隐孢子虫之间的详细相互作用，进行了大规模的无标记蛋白质组学研究，以表征微小隐孢子虫感染引起的蛋白质组变化。在鉴定的 4406 种蛋白质中，有 121 种蛋白质在微小隐孢子虫感染的 HCT-8 细胞中与未感染细胞相比差异丰富（> 1.5 倍截值，P < 0.05）。其中，感染后 36 小时有 67 种蛋白质上调，54 种蛋白质下调。差异丰富蛋白质的分析显示，宿主细胞对微小隐孢子虫感染的免疫反应以干扰素为中心，感染导致宿主细胞中代谢相关酶的广泛抑制。使用定量实时逆转录聚合酶链反应和蛋白质印迹法进一步验证了几种蛋白质。对微小隐孢子虫感染的 HCT-8 细胞的蛋白质组学进行的系统分析确定了广泛的功能蛋白，这些蛋白参与宿主抗寄生虫免疫或在感染过程中作为潜在靶标发挥作用，为微小隐孢子虫感染的分子机制提供了新的见解。
