Cryptosporidium infection of human small intestinal epithelial cells induces type III interferon and impairs infectivity of Rotavirus

Valentin Greigert, Iti Saraav, Juhee Son, Yinxing Zhu, Denise Dayao, Avan Antia, Saul Tzipori, William H. Witola, Thaddeus S. Stappenbeck, Siyuan Ding, L. David Sibley

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Cryptosporidiosis is a major cause of severe diarrheal disease in infants from resource poor settings. The majority of infections are caused by the human-specific pathogen C. hominis and absence of in vitro growth platforms has limited our understanding of host-pathogen interactions and development of effective treatments. To address this problem, we developed a stem cell-derived culture system for C. hominis using human enterocytes differentiated under air-liquid interface (ALI) conditions. Human ALI cultures supported robust growth and complete development of C. hominis in vitro including all life cycle stages. Cryptosporidium infection induced a strong interferon response from enterocytes, possibly driven, in part, by an endogenous dsRNA virus in the parasite. Prior infection with Cryptosporidium induced type III IFN secretion and consequently blunted infection with Rotavirus, including live attenuated vaccine strains. The development of hALI provides a platform for further studies on human-specific pathogens, including clinically important coinfections that may alter vaccine efficacy.

Original languageEnglish
Article number2297897
JournalGut microbes
Volume16
Issue number1
DOIs
StatePublished - 2024

Keywords

  • Vaccine
  • antiviral
  • co-infection
  • enteric infection
  • interferon
  • mucosal immunity
  • parasitology

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