IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-37129-0.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-37129-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-37129-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Merve Mutlu & Isabel Schmidt & Andrew I. Morrison & Benedikt Goretzki & Felix Freuler & Damien Begue & Oliver Simic & Nicolas Pythoud & Erik Ahrne & Sandra Kapps & Susan Roest & Debora Bonenfant & Del, 2024. "Small molecule induced STING degradation facilitated by the HECT ligase HERC4," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Zhibin Lin & Peijun Yang & Yufeng Hu & Hao Xu & Juanli Duan & Fei He & Kefeng Dou & Lin Wang, 2023. "RING finger protein 13 protects against nonalcoholic steatohepatitis by targeting STING-relayed signaling pathways," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Mutian Jia & Li Chai & Jie Wang & Mengge Wang & Danhui Qin & Hui Song & Yue Fu & Chunyuan Zhao & Chengjiang Gao & Jihui Jia & Wei Zhao, 2024. "S-nitrosothiol homeostasis maintained by ADH5 facilitates STING-dependent host defense against pathogens," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    4. Katelyn C. Cook & Elene Tsopurashvili & Jason M. Needham & Sunnie R. Thompson & Ileana M. Cristea, 2022. "Restructured membrane contacts rewire organelles for human cytomegalovirus infection," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    5. Chiara Scopa & Samantha M. Barnada & Maria E. Cicardi & Mo Singer & Davide Trotti & Marco Trizzino, 2023. "JUN upregulation drives aberrant transposable element mobilization, associated innate immune response, and impaired neurogenesis in Alzheimer’s disease," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Jeremy J. Ratiu & William E. Barclay & Elliot Lin & Qun Wang & Sebastian Wellford & Naren Mehta & Melissa J. Harnois & Devon DiPalma & Sumedha Roy & Alejandra V. Contreras & Mari L. Shinohara & David , 2022. "Loss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-β selection thymocytes," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    7. Martha Triantafilou & Joshi Ramanjulu & Lee M. Booty & Gisela Jimenez-Duran & Hakan Keles & Ken Saunders & Neysa Nevins & Emma Koppe & Louise K. Modis & G. Scott Pesiridis & John Bertin & Kathy Triant, 2022. "Human rhinovirus promotes STING trafficking to replication organelles to promote viral replication," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    8. Mutian Jia & Yuanyuan Wang & Jie Wang & Danhui Qin & Mengge Wang & Li Chai & Yue Fu & Chunyuan Zhao & Chengjiang Gao & Jihui Jia & Wei Zhao, 2023. "Myristic acid as a checkpoint to regulate STING-dependent autophagy and interferon responses by promoting N-myristoylation," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    9. Matteo Gentili & Bingxu Liu & Malvina Papanastasiou & Deborah Dele-Oni & Marc A. Schwartz & Rebecca J. Carlson & Aziz M. Al’Khafaji & Karsten Krug & Adam Brown & John G. Doench & Steven A. Carr & Nir , 2023. "ESCRT-dependent STING degradation inhibits steady-state and cGAMP-induced signalling," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    10. Haruka Kemmoku & Kanoko Takahashi & Kojiro Mukai & Toshiki Mori & Koichiro M. Hirosawa & Fumika Kiku & Yasunori Uchida & Yoshihiko Kuchitsu & Yu Nishioka & Masaaki Sawa & Takuma Kishimoto & Kazuma Tan, 2024. "Single-molecule localization microscopy reveals STING clustering at the trans-Golgi network through palmitoylation-dependent accumulation of cholesterol," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    11. Maritza Puray-Chavez & Jenna E. Eschbach & Ming Xia & Kyle M. LaPak & Qianzi Zhou & Ria Jasuja & Jiehong Pan & Jian Xu & Zixiang Zhou & Shawn Mohammed & Qibo Wang & Dana Q. Lawson & Sanja Djokic & Gao, 2024. "A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    12. Hervé Técher & Diyavarshini Gopaul & Jonathan Heuzé & Nail Bouzalmad & Baptiste Leray & Audrey Vernet & Clément Mettling & Jérôme Moreaux & Philippe Pasero & Yea-Lih Lin, 2024. "MRE11 and TREX1 control senescence by coordinating replication stress and interferon signaling," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    13. Sarah Rösing & Fabian Ullrich & Susann Meisterfeld & Franziska Schmidt & Laura Mlitzko & Marijana Croon & Ryan G Nattrass & Nadia Eberl & Julia Mahlberg & Martin Schlee & Anja Wieland & Philipp Simon , 2024. "Chronic endoplasmic reticulum stress in myotonic dystrophy type 2 promotes autoimmunity via mitochondrial DNA release," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    14. Kaiyuan Wang & Yang Li & Xia Wang & Zhijun Zhang & Liping Cao & Xiaoyuan Fan & Bin Wan & Fengxiang Liu & Xuanbo Zhang & Zhonggui He & Yingtang Zhou & Dong Wang & Jin Sun & Xiaoyuan Chen, 2023. "Gas therapy potentiates aggregation-induced emission luminogen-based photoimmunotherapy of poorly immunogenic tumors through cGAS-STING pathway activation," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    15. Joana Sá-Pessoa & Sara López-Montesino & Kornelia Przybyszewska & Isabel Rodríguez-Escudero & Helina Marshall & Adelia Ova & Gunnar N. Schroeder & Peter Barabas & María Molina & Tim Curtis & Víctor J., 2023. "A trans-kingdom T6SS effector induces the fragmentation of the mitochondrial network and activates innate immune receptor NLRX1 to promote infection," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    16. Xiaolan Liu & Xufeng Cen & Ronghai Wu & Ziyan Chen & Yanqi Xie & Fengqi Wang & Bing Shan & Linghui Zeng & Jichun Zhou & Bojian Xie & Yangjun Cai & Jinyan Huang & Yingjiqiong Liang & Youqian Wu & Chao , 2023. "ARIH1 activates STING-mediated T-cell activation and sensitizes tumors to immune checkpoint blockade," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37129-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.