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

Mucosal Immunol. 2014 Jan;7(1):57-67. doi: 10.1038/mi.2013.24. Epub 2013 Apr 24.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Gene Expression Regulation
  • Humans
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology
  • Intestines / immunology
  • Intestines / microbiology
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Knockout
  • Permeability
  • Protein Binding
  • Protein Kinase C / metabolism*
  • Protein Transport
  • Receptors, Interleukin-1 / deficiency
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / metabolism*
  • Salmonella Infections / genetics
  • Salmonella Infections / immunology
  • Salmonella Infections / metabolism
  • Salmonella Infections / microbiology
  • Salmonella typhimurium / immunology
  • Signal Transduction
  • Tight Junction Proteins / genetics
  • Tight Junction Proteins / metabolism


  • Membrane Glycoproteins
  • Receptors, Interleukin-1
  • TIRAP protein, mouse
  • Tight Junction Proteins
  • Protein Kinase C