The beta 6 Integrin Negatively Regulates TLR7-Mediated Epithelial Immunity via Autophagy During Influenza A Virus Infection

Smith, M.; Meliopoulos, V. A.; Tan, S.; Bub, T.; Brigleb, P. H.; Sharp, B.; Crawford, J. C.; Prater, M. S.; Pruett-Miller, S. M.; Schultz-Cherry, S.

doi:10.1101/2023.08.28.555098

bioRxiv · 10.1101/2023.08.28.555098

The beta 6 Integrin Negatively Regulates TLR7-Mediated Epithelial Immunity via Autophagy During Influenza A Virus Infection

Smith, M.·Meliopoulos, V. A.·Tan, S.·Bub, T.·Brigleb, P. H.·Sharp, B.·Crawford, J. C.·Prater, M. S.·Pruett-Miller, S. M.·Schultz-Cherry, S.

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Abstract

Integrins are essential surface receptors that sense extracellular changes to initiate various intracellular signaling cascades. The rapid activation of the epithelial-intrinsic {beta}6 integrin during influenza A virus (IAV) infection has been linked to innate immune impairments. Yet, how {beta}6 regulates epithelial immunity remains undefined. Here, we identify the role of {beta}6 in mediating the Toll-like receptor 7 (TLR7) through the regulation of intracellular trafficking. We demonstrate that deletion of the {beta}6 integrin in lung epithelial cells significantly enhances the TLR7-mediated activation of the type I interferon (IFN) response during homeostasis and respiratory infection. IAV-induced {beta}6 facilitates TLR7 trafficking to lysosome-associated membrane protein (LAMP2a) components, leading to a reduction in endosomal compartments and associated TLR7 signaling. Our findings reveal an unappreciated role of {beta}6-induced autophagy in influencing epithelial immune responses during influenza virus infection.

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Smith, M., Meliopoulos, V. A., Tan, S., Bub, T., Brigleb, P. H., Sharp, B., Crawford, J. C., Prater, M. S., Pruett-Miller, S. M., Schultz-Cherry, S.. 2023-08-28. The beta 6 Integrin Negatively Regulates TLR7-Mediated Epithelial Immunity via Autophagy During Influenza A Virus Infection. https://doi.org/10.1101/2023.08.28.555098

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