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

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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

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Protein Kinase C
Infection
Tight Junctions
Intestinal Mucosa
Permeability
Claudin-3
Occludin
Protein C Inhibitor
Salmonella typhimurium
Protein Kinase Inhibitors
Electric Impedance
Protein Isoforms
Mucous Membrane
Bone Marrow

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Corr, S. C., Palsson-Mcdermott, E. M., Grishina, I., Barry, S. P., Aviello, G., Bernard, N. J., ... 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

MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C. / 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, Satya; Fallon, P. G.; O'Neill, L. A J.

In: Mucosal Immunology, Vol. 7, No. 1, 01.2014, p. 57-67.

Research output: Contribution to journalArticle

Corr, SC, Palsson-Mcdermott, EM, Grishina, I, Barry, SP, Aviello, G, Bernard, NJ, Casey, PG, Ward, JBJ, Keely, SJ, Dandekar, S, Fallon, PG & O'Neill, LAJ 2014, 'MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C', Mucosal Immunology, vol. 7, no. 1, pp. 57-67. https://doi.org/10.1038/mi.2013.24
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, Satya ; Fallon, P. G. ; O'Neill, L. A J. / MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C. In: Mucosal Immunology. 2014 ; Vol. 7, No. 1. pp. 57-67.
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