Asymmetric distribution of TLR3 leads to a polarized immune response in human intestinal epithelial cells

Megan L. Stanifer*, Markus Mukenhirn, Stephanie Muenchau, Kalliopi Pervolaraki, Takashi Kanaya, Dorothee Albrecht, Charlotte Odendall, Thomas Hielscher, Volker Haucke, Jonathan C. Kagan, Sina Bartfeld, Hiroshi Ohno, Steeve Boulant

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)181-191
Number of pages11
JournalNature Microbiology
Volume5
Issue number1
DOIs
Publication statusPublished - 1 Jan 2020

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