Trusting a gut feeling: the potential of a newly refined human intestinal enteroid model to evaluate viral‐host interactions

Autor: Coish, Jeremia M., Crozier, Robert W. E., Schertzer, Katarina E.
Rok vydání: 2020
Předmět:
Zdroj: The Journal of Physiology
J Physiol
ISSN: 1469-7793
0022-3751
Popis: The intestinal epithelium represents the primary interface between the host, the gut microbiome and its external environment. Since the intestinal epithelium contributes to innate immunity as a first line of defense, understanding how the epithelium responds to microbial and host stimuli is an important consideration in promoting homeostasis. Human intestinal enteroids (HIEs) are primary epithelial cell cultures that can provide insights into the biology of the intestinal epithelium and innate immune responses. One potential limitation of using HIEs for innate immune studies is the relative lack of responsiveness to factors that stimulate epithelial cytokine production. We report technical refinements, including removal of extracellular antioxidants, to facilitate enhanced cytokine responses in HIEs. Using this new method, we demonstrate that HIEs have distinct cytokine profiles in response to pro-inflammatory stimuli derived from host and microbial sources. Overall, we found that host-derived cytokines TNF and IL-1α stimulated reactive oxygen species and a large repertoire of cytokines. In contrast, microbial stimuli LPS, LTA and flagellin stimulated a limited number of cytokines and histamine did not stimulate the release of any cytokines. Importantly HIE secreted cytokines were functionally active, as denoted by the ability of human blood-derived neutrophil to migrate towards HIE supernatant containing IL-8. These findings establish that the immune responsiveness of HIEs depends on medium composition and stimuli. By refining the experimental culture medium and creating an environment conducive to epithelial cytokine responses by human enteroids, HIEs can facilitate exploration of many experimental questions pertaining to the role of the intestinal epithelium in innate immunity.
Databáze: OpenAIRE
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