MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C

S. C. Corr, E. M. Palsson-Mcdermott, I. Grishina, S. P. Barry, G. Aviello, N. J. Bernard, P. G. Casey, J. B J Ward, S. J. Keely, Satya Dandekar, P. G. Fallon, L. A J O'Neill

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

MyD88 adapter-like (Mal)-deficient mice displayed increased susceptibility to oral but not intraperitoneal infection with Salmonella Typhimurium. Bone marrow chimeras demonstrated that mice with Mal-deficient non-hematopoietic cells were more susceptible to infection, indicating a role for Mal in non-myeloid cells. We observed perturbed barrier function in Mal-/- mice, as indicated by reduced electrical resistance and increased mucosa blood permeability following infection. Altered expression of occludin, Zonula occludens-1, and claudin-3 in intestinal epithelia from Mal-/- mice suggest that Mal regulates tight junction formation, which may in part contribute to intestinal integrity. Mal interacted with several protein kinase C (PKC) isoforms in a Caco-2 model of intestinal epithelia and inhibition of Mal or PKC increased permeability and bacterial invasion via a paracellular route, while a pan-PKC inhibitor increased susceptibility to oral infection in mice. Mal signaling is therefore beneficial to the integrity of the intestinal barrier during infection.

Original languageEnglish (US)
Pages (from-to)57-67
Number of pages11
JournalMucosal Immunology
Volume7
Issue number1
DOIs
StatePublished - Jan 2014

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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    Corr, S. C., Palsson-Mcdermott, E. M., Grishina, I., Barry, S. P., Aviello, G., Bernard, N. J., Casey, P. G., Ward, J. B. J., Keely, S. J., Dandekar, S., Fallon, P. G., & O'Neill, L. A. J. (2014). MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C. Mucosal Immunology, 7(1), 57-67. https://doi.org/10.1038/mi.2013.24