TY  - JOUR
AU  - Stanifer, Megan
AU  - Mukenhirn, Markus
AU  - Muenchau, Stephanie
AU  - Pervolaraki, Kalliopi
AU  - Kanaya, Takashi
AU  - Albrecht, Dorothee
AU  - Odendall, Charlotte
AU  - Hielscher, Thomas
AU  - Haucke, Volker
AU  - Kagan, Jonathan C
AU  - Bartfeld, Sina
AU  - Ohno, Hiroshi
AU  - Boulant, Steeve
TI  - Asymmetric distribution of TLR3 leads to a polarized immune response in human intestinal epithelial cells.
JO  - Nature microbiology
VL  - 5
IS  - 1
SN  - 2058-5276
CY  - London
PB  - Nature Publishing Group
M1  - DKFZ-2019-03173
SP  - 181-191
PY  - 2020
N1  - 2020 Jan;5(1):181-191#EA:F140#LA:F140#
AB  - Intestinal epithelial cells (IECs) act as a physical barrier separating the commensal-containing intestinal tract from the sterile interior. These cells have found a complex balance allowing them to be prepared for pathogen attacks while still tolerating the presence of bacterial or viral stimuli present in the lumen of the gut. Using primary human IECs, we probed the mechanisms that allow for such a tolerance. We discovered that viral infections emanating from the basolateral side of IECs elicit a stronger intrinsic immune response in comparison to lumenal apical infections. We determined that this asymmetric immune response is driven by the clathrin-sorting adaptor AP-1B, which mediates the polarized sorting of Toll-like receptor 3 (TLR3) towards the basolateral side of IECs. Mice and human IECs lacking AP-1B showed an exacerbated immune response following apical stimulation. Together, these results suggest a model where the cellular polarity program plays an integral role in the ability of IECs to partially tolerate apical commensals while remaining fully responsive to invasive basolateral pathogens.
LB  - PUB:(DE-HGF)16
C6  - pmid:31686029
DO  - DOI:10.1038/s41564-019-0594-3
UR  - https://inrepo02.dkfz.de/record/148628
ER  -