論文

査読有り 国際誌
2020年1月

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

Nature microbiology
  • 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

5
1
開始ページ
181
終了ページ
191
記述言語
英語
掲載種別
DOI
10.1038/s41564-019-0594-3

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.

リンク情報
DOI
https://doi.org/10.1038/s41564-019-0594-3
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31686029

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