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

Author

Listed:
  • Silu Deng

    (Rush University Medical Center
    Creighton University School of Medicine)

  • Wei He

    (Creighton University School of Medicine)

  • Ai-Yu Gong

    (Rush University Medical Center
    Creighton University School of Medicine)

  • Min Li

    (Creighton University School of Medicine)

  • Yang Wang

    (Creighton University School of Medicine)

  • Zijie Xia

    (Creighton University School of Medicine)

  • Xin-Tiang Zhang

    (Creighton University School of Medicine)

  • Andrew S. Huang Pacheco

    (University of Nebraska Medical Center)

  • Ankur Naqib

    (Rush University Medical Center)

  • Mark Jenkins

    (the United States Department of Agriculture)

  • Patrick C. Swanson

    (Creighton University School of Medicine)

  • Kristen M. Drescher

    (Creighton University School of Medicine)

  • Juliane K. Strauss-Soukup

    (Creighton University College of Arts and Sciences)

  • Michael Belshan

    (Creighton University School of Medicine)

  • Xian-Ming Chen

    (Rush University Medical Center
    Creighton University School of Medicine)

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.

Suggested Citation

  • Silu Deng & Wei He & Ai-Yu Gong & Min Li & Yang Wang & Zijie Xia & Xin-Tiang Zhang & Andrew S. Huang Pacheco & Ankur Naqib & Mark Jenkins & Patrick C. Swanson & Kristen M. Drescher & Juliane K. Straus, 2023. "Cryptosporidium uses CSpV1 to activate host type I interferon and attenuate antiparasitic defenses," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37129-0
    DOI: 10.1038/s41467-023-37129-0
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    References listed on IDEAS

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    1. Simone M. Haag & Muhammet F. Gulen & Luc Reymond & Antoine Gibelin & Laurence Abrami & Alexiane Decout & Michael Heymann & F. Gisou van der Goot & Gerardo Turcatti & Rayk Behrendt & Andrea Ablasser, 2018. "Targeting STING with covalent small-molecule inhibitors," Nature, Nature, vol. 559(7713), pages 269-273, July.
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