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, S Dandekar, P G Fallon, L A J O'Neill

Research output: Contribution to journalArticle

21 Citations (Scopus)

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
Pages (from-to)57-67
Number of pages11
JournalMucosal Immunology
Volume7
Issue number1
Early online date24 Apr 2013
DOIs
Publication statusPublished - Jan 2014

Keywords

  • Animals
  • Cell Line
  • Gene Expression Regulation
  • Humans
  • Intestinal Mucosa
  • Intestines
  • Membrane Glycoproteins
  • Mice
  • Mice, Knockout
  • Permeability
  • Protein Binding
  • Protein Kinase C
  • Protein Transport
  • Receptors, Interleukin-1
  • Salmonella Infections
  • Salmonella typhimurium
  • Signal Transduction
  • Tight Junction Proteins
  • Journal Article
  • Research Support, Non-U.S. Gov't

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