1. Cryptosporidium uses CSpV1 to activate host type I interferon and attenuate antiparasitic defenses.
- Author
-
Deng S, He W, Gong AY, Li M, Wang Y, Xia Z, Zhang XT, Huang Pacheco AS, Naqib A, Jenkins M, Swanson PC, Drescher KM, Strauss-Soukup JK, Belshan M, and Chen XM
- Subjects
- Animals, Mice, Antiparasitic Agents metabolism, Antiparasitic Agents pharmacology, Cryptosporidium pathogenicity, Cryptosporidium virology, Double Stranded RNA Viruses metabolism, Cryptosporidiosis etiology, Cryptosporidiosis parasitology, Cryptosporidiosis virology, Cryptosporidium parvum pathogenicity, Cryptosporidium parvum virology, Host-Parasite Interactions genetics, Interferon Type I metabolism, Interferon Type I pharmacology
- Abstract
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., (© 2023. The Author(s).)- Published
- 2023
- Full Text
- View/download PDF