Infection of Human Small Intestinal Epithelial Cells Induces Type III Interferon and Impairs Infectivity of Rotavirus

Overview

Journal Gut Microbes

Specialties Gastroenterology
Microbiology

Date 2024 Jan 8

PMID 38189373

Authors

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

Affiliations

Soon will be listed here.

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 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 using human enterocytes differentiated under air-liquid interface (ALI) conditions. Human ALI cultures supported robust growth and complete development of in vitro including all life cycle stages. infection induced a strong interferon response from enterocytes, possibly driven, in part, by an endogenous dsRNA virus in the parasite. Prior infection with 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.

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