@article{bfb97f80d3a2487886360a6861463261,
title = "Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis",
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. ",
author = "Ladinsky, {Mark S.} and Araujo, {Leandro P.} and Xiao Zhang and John Veltri and Marta Galan-Diez and Salima Soualhi and Carolyn Lee and Koichiro Irie and Pinker, {Elisha Y.} and Seiko Narushima and Sheila Bandyopadhyay and Manabu Nagayama and Wael Elhenawy and Coombes, {Brian K.} and Ferraris, {Ronaldo P.} and Kenya Honda and Iliev, {Iliyan D.} and Nan Gao and Bjorkman, {Pamela J.} and Ivanov, {Ivaylo I.}",
note = "Funding Information: We thank D. Littman (NYU) for generously providing 7B8 Tg mice and anti-P3340 antibody. We thank Y. Zheng (Cincinnati Children{\textquoteright}s Hospital) for providing CDC42-flox mice. We thank C. Jobin (University of Florida) for providing AIEC strain LF82. We thank E. Byington from the JP Sulzberger Columbia Genome Center for help with RNA-seq analysis. We thank members of the Ivanov and Gao laboratories for technical help. We thank S. Ghosh and S. Reiner for providing advice and feedback throughout the project and for help with the manuscript. We thank E. Reeder from LNinnovations and M. Murphy for assistance with illustrations. Funding: This work was supported by funding from the following sources: NIH R21 AI126305 and R01 DK098378 (I.I.I.); P50 GM082545 (P.J.B); NIH R01 DK102934 and ACS Research Scholar Award 15-060-01-TBE (N.G.); NSF/BIO/IOS 1456673 (R.P.F.); NIH R01 AT010243 (N.G. and R.P.F.); AMED-LEAP JP17 g0010003 and Takeda Science Foundation (K.H.); CIHR Grant 324932 (B.K.C.); Columbia University Schaefer Research Award (I.I.I.); and Pew Charitable Trust Innovation Fund Award 00031379 (I.I.I and P.J.B.). Publisher Copyright: 2017 {\textcopyright} The Authors.",
year = "2019",
doi = "10.1126/science.aat4042",
language = "English",
volume = "363",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6431",
}