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

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 Strauss-Soukup; Michael Belshan; Xian-Ming Chen

doi:10.1038/s41467-023-37129-0

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

Journal article

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

Silu Deng, Wei He, Ai-Yu Gong, Min Li, Yang Wang, Zijie Xia, Xin-Tiang Zhang, Andrew S Huang Pacheco, Ankur Naqib, Mark Jenkins, …

Nature communications, Vol.14(1), pp.1456-17

03/16/2023

DOI: https://doi.org/10.1038/s41467-023-37129-0

PMID: 36928642

Abstract

Animals

Antiparasitic Agents - metabolism

Antiparasitic Agents - pharmacology

Cryptosporidiosis - etiology

Cryptosporidiosis - parasitology

Cryptosporidiosis - virology

Cryptosporidium - pathogenicity

Cryptosporidium - virology

Cryptosporidium parvum - pathogenicity

Cryptosporidium parvum - virology

Double Stranded RNA Viruses - metabolism

Host-Parasite Interactions - genetics

Interferon Type I - metabolism

Interferon Type I - pharmacology

Mice

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.

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Title: Cryptosporidium uses CSpV1 to activate host type I interferon and attenuate antiparasitic defenses
Creators: Silu Deng - Rush University Medical Center
Wei He - Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE, USA
Ai-Yu Gong - Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE, USA
Min Li - Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE, USA
Yang Wang - Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE, USA
Zijie Xia - Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE, USA
Xin-Tiang Zhang - Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE, USA
Andrew S Huang Pacheco - University of Nebraska Medical Center
Ankur Naqib - Rush University Medical Center
Mark Jenkins - Animal Parasitic Diseases Laboratory, Agricultural Research Service, the United States Department of Agriculture, Beltsville, MD, USA
Patrick C Swanson - Creighton University
Kristen M Drescher - Creighton University
Juliane K Strauss-Soukup - Creighton University
Michael Belshan - Creighton University
Xian-Ming Chen - Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE, USA. xian_m_chen@rush.edu
Publication Details: Nature communications, Vol.14(1), pp.1456-17
Grant note: AI156370 / Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) AI136877 / Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) R21 AI141325 / NIAID NIH HHS AI116323 / Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) R21 AI156370 / NIAID NIH HHS R01 AI136877 / NIAID NIH HHS AI141325 / Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) R01 AI116323 / NIAID NIH HHS
Identifiers: 991005968541902656
Academic Unit: Creighton University; Chemistry and Biochemistry; Med. Microbiology & Immunology
Language: English
Resource Type: Journal article

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

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