Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis

Mark S. Ladinsky, Leandro P. Araujo, Xiao Zhang, John Veltri, Marta Galan-Diez, Salima Soualhi, Carolyn Lee, Koichiro Irie, Elisha Y. Pinker, Seiko Narushima, Sheila Bandyopadhyay, Manabu Nagayama, Wael Elhenawy, Brian K. Coombes, Ronaldo P. Ferraris, Kenya Honda, Iliyan D. Iliev, Nan Gao, Pamela J. Bjorkman, Ivaylo I. Ivanov

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22 Citations (Scopus)

Abstract

Commensal bacteria influence host physiology, without invading host tissues. We show that proteins from segmented filamentous bacteria (SFB) are transferred into intestinal epithelial cells (IECs) through adhesion-directed endocytosis that is distinct from the clathrin-dependent endocytosis of invasive pathogens. This process transfers microbial cell wall–associated proteins, including an antigen that stimulates mucosal T helper 17 (T H 17) cell differentiation, into the cytosol of IECs in a cell division control protein 42 homolog (CDC42)–dependent manner. Removal of CDC42 activity in vivo led to disruption of endocytosis induced by SFB and decreased epithelial antigen acquisition, with consequent loss of mucosal T H 17 cells. Our findings demonstrate direct communication between a resident gut microbe and the host and show that under physiological conditions, IECs acquire antigens from commensal bacteria for generation of T cell responses to the resident microbiota.

Original languageEnglish
Article numbereaat4042
JournalScience
Volume363
Issue number6431
DOIs
Publication statusPublished - 2019 Jan 1

ASJC Scopus subject areas

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    Ladinsky, M. S., Araujo, L. P., Zhang, X., Veltri, J., Galan-Diez, M., Soualhi, S., Lee, C., Irie, K., Pinker, E. Y., Narushima, S., Bandyopadhyay, S., Nagayama, M., Elhenawy, W., Coombes, B. K., Ferraris, R. P., Honda, K., Iliev, I. D., Gao, N., Bjorkman, P. J., & Ivanov, I. I. (2019). Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis. Science, 363(6431), [eaat4042]. https://doi.org/10.1126/science.aat4042