Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
PLoS Pathog. 2024 May 8;20(5):e1011820. doi: 10.1371/journal.ppat.1011820. eCollection 2024 May.
The production of IFN-γ is crucial for control of multiple enteric infections, but its impact on intestinal epithelial cells (IEC) is not well understood. Cryptosporidium parasites exclusively infect epithelial cells and the ability of interferons to activate the transcription factor STAT1 in IEC is required for parasite clearance. Here, the use of single cell RNA sequencing to profile IEC during infection revealed an increased proportion of mid-villus enterocytes during infection and induction of IFN-γ-dependent gene signatures that was comparable between uninfected and infected cells. These analyses were complemented by in vivo studies, which demonstrated that IEC expression of the IFN-γ receptor was required for parasite control. Unexpectedly, treatment of Ifng-/- mice with IFN-γ showed the IEC response to this cytokine correlates with a delayed reduction in parasite burden but did not affect parasite development. These data sets provide insight into the impact of IFN-γ on IEC and suggest a model in which IFN-γ signalling to uninfected enterocytes is important for control of Cryptosporidium.
IFN-γ 的产生对于控制多种肠道感染至关重要，但它对肠上皮细胞（IEC）的影响尚不清楚。隐孢子虫寄生虫专门感染上皮细胞，干扰素激活 IEC 中转录因子 STAT1 的能力是清除寄生虫所必需的。在这里，使用单细胞 RNA 测序在感染过程中对 IEC 进行分析，发现在感染期间中绒毛上皮细胞的比例增加，并且诱导了 IFN-γ 依赖性基因特征，在未感染和感染细胞之间是可比的。这些分析得到了体内研究的补充，这些研究表明，IEC 表达 IFN-γ 受体是控制寄生虫所必需的。出乎意料的是，用 IFN-γ 治疗 Ifng-/- 小鼠表明，该细胞因子对 IEC 的反应与寄生虫负荷的延迟减少相关，但不影响寄生虫的发育。这些数据集提供了 IFN-γ 对 IEC 的影响的见解，并提出了一个模型，其中 IFN-γ 信号转导到未感染的肠上皮细胞对于控制隐孢子虫很重要。
