Toxoplasma gondii Infection Promotes Epithelial Barrier Dysfunction of Caco-2 Cells

J Histochem Cytochem. 2016 Aug;64(8):459-69. doi: 10.1369/0022155416656349. Epub 2016 Jul 1.

Abstract

After oral infection, Toxoplasma gondii invades intestinal cells, induces breakdown of intestinal physiology and barrier functions, and causes intestinal pathology in some animal species. Although parasites' invasion into host cells is a known phenomenon, the effects of T. gondii infection in the intestinal barrier are still not well established. To evaluate morphological and physiological modifications on the colorectal adenocarcinoma-derived Caco-2 cell line during T. gondii infection, microvilli, tight junction integrity, and transepithelial electrical resistance (TEER) were investigated under infection. It was observed that the dextran uptake (endocytosis) and distribution were smaller in infected than in noninfected Caco-2 cells. The infection leads to the partial loss of microvilli at the cell surface. Claudin-1, zonula occludens-1 (ZO-1), and occludin expressions were colocalized by immunofluorescence and presented discontinuous net patterns in infected cells. Immunoblotting analysis at 24 hr postinfection revealed decreasing expression of occludin and ZO-1 proteins, whereas claudin-1 presented similar expression level compared with noninfected cells. T. gondii decreased TEER in Caco-2 cells 24 hr after infection. Our results suggest that T. gondii infection may lead to the loss of integrity of intestinal mucosa, resulting in impaired barrier function.

Keywords: Caco-2 cells; Toxoplasma gondii; epithelial barrier dysfunction; tight junctions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / ultrastructure
  • Caco-2 Cells
  • Cell Polarity
  • Claudin-1 / metabolism
  • Dextrans / metabolism
  • Electric Impedance
  • Endocytosis
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / parasitology*
  • Intestinal Mucosa / ultrastructure
  • Microvilli / metabolism
  • Microvilli / parasitology
  • Microvilli / ultrastructure
  • Occludin / metabolism
  • Tight Junctions / metabolism
  • Tight Junctions / parasitology
  • Tight Junctions / ultrastructure
  • Toxoplasma / physiology*
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Claudin-1
  • Dextrans
  • Occludin
  • TJP1 protein, human
  • Zonula Occludens-1 Protein