Modulation of epithelial immunity by mucosal fluid.

Scientific Reports
James J MunSuzanne M J Fleiszig

Abstract

Mucosal epithelial cells, including those at the ocular surface, resist infection by most microbes in vivo but can be susceptible to microbial virulence in vitro. While fluids bathing mucosal surfaces (e.g. tears) contain antimicrobials, potentially pathogenic microbes often thrive in these fluids, suggesting that additional mechanisms mediate epithelial resistance in vivo. Here, tear fluid acted directly upon epithelial cells to enhance their resistance to bacterial invasion and cytotoxicity. Resistance correlated with tear fluid-magnified activation of NFκB and AP-1 transcription factors in epithelial cells in response to bacterial antigens, suggesting priming of innate defense pathways. Further analysis revealed differential regulation of potential epithelial cell defense genes by tears. siRNA knockdown confirmed involvement of at least two factors, RNase7 and ST-2, for which tears increased mRNA levels, in protection against bacterial invasion. Thus, the role of mucosal fluids in defense can include modulation of epithelial immunity, in addition to direct effects on microbes.

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Citations

Jul 25, 2013·Experimental Eye Research·Alison M McDermott
Dec 26, 2012·Eye & Contact Lens·David J Evans, Suzanne M J Fleiszig
Dec 15, 2015·Autoimmunity Reviews·Francisco Assis de AndradeRoger Abramino Levy
Apr 23, 2013·American Journal of Ophthalmology·David J Evans, Suzanne M J Fleiszig
Jan 22, 2017·Immunology·Jeremías G GallettiMirta N Giordano
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Sep 20, 2019·Microorganisms·Shunbin Xu, Linda D Hazlett
Nov 23, 2019·Progress in Retinal and Eye Research·Suzanne M J FleiszigDavid J Evans
Jun 8, 2021·Experimental Eye Research·Lawson Ung, James Chodosh
Sep 28, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Stephanie J WanSuzanne M J Fleiszig

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Methods Mentioned

BETA
transfection

Software Mentioned

FluorChem Q SA
Affymetrix
Microarray Suite ( MAS )
Bioconductor

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