隐孢子虫利用 CSpV1 激活宿主 I 型干扰素并减弱抗寄生虫防御。

Cryptosporidium uses CSpV1 to activate host type I interferon and attenuate antiparasitic defenses.

机构信息

Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL, USA.

Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE, USA.

出版信息

Nat Commun. 2023 Mar 16;14(1):1456. doi: 10.1038/s41467-023-37129-0.

Cryptosporidium infects gastrointestinal epithelium and is a leading cause of infectious diarrhea and diarrheal-related death in children worldwide. There are no vaccines and no fully effective therapy available for the infection. Type II and III interferon (IFN) responses are important determinants of susceptibility to infection but the role for type I IFN response remains obscure. Cryptosporidium parvum virus 1 (CSpV1) is a double-stranded RNA (dsRNA) virus harbored by Cryptosporidium spp. Here we show that intestinal epithelial conditional Ifnar1 mice (deficient in type I IFN receptor) are resistant to C. parvum infection. CSpV1-dsRNAs are delivered into host cells and trigger type I IFN response in infected cells. Whereas C. parvum infection attenuates epithelial response to IFN-γ, loss of type I IFN signaling or inhibition of CSpV1-dsRNA delivery can restore IFN-γ-mediated protective response. Our findings demonstrate that type I IFN signaling in intestinal epithelial cells is detrimental to intestinal anti-C. parvum defense and Cryptosporidium uses CSpV1 to activate type I IFN signaling to evade epithelial antiparasitic response.

隐孢子虫感染胃肠道上皮细胞，是全世界导致传染性腹泻和腹泻相关死亡的主要原因。目前尚无针对该感染的疫苗和完全有效的治疗方法。II 型和 III 型干扰素（IFN）反应是决定易感性的重要因素，但 I 型 IFN 反应的作用仍不清楚。微小隐孢子虫病毒 1（CSpV1）是一种双链 RNA（dsRNA）病毒，存在于隐孢子虫属中。在这里，我们发现肠道上皮细胞条件性 Ifnar1 小鼠（缺乏 I 型 IFN 受体）对微小隐孢子虫感染具有抗性。CSpV1-dsRNA 被递送到宿主细胞中，并在感染细胞中引发 I 型 IFN 反应。虽然微小隐孢子虫感染会减弱上皮细胞对 IFN-γ的反应，但缺失 I 型 IFN 信号或抑制 CSpV1-dsRNA 的递呈均可恢复 IFN-γ介导的保护反应。我们的研究结果表明，肠道上皮细胞中的 I 型 IFN 信号对肠道抗微小隐孢子虫防御有害，而隐孢子虫利用 CSpV1 激活 I 型 IFN 信号以逃避上皮细胞的抗寄生虫反应。