Cellular polarity asymmetrically functionalizes pathogen recognition receptor-mediated intrinsic immune response in human intestinal epithelium cells

Stanifer, M.; Muenchau, S.; Pervolaraki, K.; Kanaya, T.; Mukenhirn, M.; Albrecht, D.; Odendall, C.; Kagan, J.; Bartfeld, S.; Ohno, H.; Boulant, S.

doi:10.1101/450668

bioRxiv · 10.1101/450668

Cellular polarity asymmetrically functionalizes pathogen recognition receptor-mediated intrinsic immune response in human intestinal epithelium cells

Stanifer, M.·Muenchau, S.·Pervolaraki, K.·Kanaya, T.·Mukenhirn, M.·Albrecht, D.·Odendall, C.·Kagan, J.·Bartfeld, S.·Ohno, H.·Boulant, S.

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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 bacteria/viral stimuli present in the lumen of the gut. Using primary human IECs, we probed the mechanisms, which allow for such a tolerance. We discovered that viral infection emanating from the basolateral side of IECs elicited a stronger intrinsic immune response as compared to lumenal apical infection. We determined that this asymmetric immune response was driven by the clathrin-sorting adapter AP-1B which mediates the polarized sorting of Toll-like receptor 3 (TLR3) toward 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 against invasive basolateral pathogens.

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Stanifer, M., Muenchau, S., Pervolaraki, K., Kanaya, T., Mukenhirn, M., Albrecht, D., Odendall, C., Kagan, J., Bartfeld, S., Ohno, H., Boulant, S.. 2018-10-23. Cellular polarity asymmetrically functionalizes pathogen recognition receptor-mediated intrinsic immune response in human intestinal epithelium cells. https://doi.org/10.1101/450668

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