Intestinal epithelial cells and T cells differentially recognize and respond to Candida albicans yeast and hypha

Anja Schirbel1, Dror S Shouval2,3, Betty Hebecker4,5

  • 1Department of Medicine, Division of Gastroenterology and Hepatology, Charité Campus Mitte, Universitätsmedizin Berlin, Germany.

Insights

The study investigated how Candida albicans (fungus) affects intestinal cells and immune cells in inflammatory bowel diseases (IBD). Findings show C. albicans influences cell responses differently depending on its form, impacting IBD pathogenesis.

Area of Science:

  • Gastroenterology
  • Immunology
  • Microbiology

Background:

  • Inflammatory bowel diseases (IBD) are complex disorders with increasing focus on microbial roles.
  • While bacterial involvement is well-studied, the contribution of intestinal fungi, like Candida albicans, to IBD pathogenesis remains less understood.
  • Candida albicans is a common gut fungus that may play a role in maintaining intestinal homeostasis or triggering IBD.

Purpose of the Study:

  • To investigate the differential effects of Candida albicans yeast and hyphal forms on intestinal epithelial cells and T cells.
  • To compare responses in cells from patients with IBD versus healthy individuals.
  • To elucidate the mechanisms of C. albicans recognition by host cells.

Main Methods:

  • Utilized Caco-2 intestinal epithelial cell lines and primary T cells from IBD patients and healthy controls.
  • Exposed cells to different morphologies of C. albicans (yeast and hypha).
  • Assessed cellular responses including activation, cytokine secretion, apoptosis, and proliferation, using synthetic agonists like β-glucans and Pam3CSK4 for comparison.

Main Results:

  • C. albicans elicited distinct responses from Caco-2 cells depending on its morphology (yeast vs. hypha), partly mimicked by synthetic agonists.
  • Unstimulated T cells showed increased activation and pro-inflammatory cytokine secretion upon C. albicans exposure.
  • T cells stimulated with CD3 and C. albicans exhibited reduced activation, cytokine secretion, apoptosis, and proliferation, indicating complex reciprocal interactions.
  • Glycans alone did not fully replicate the observed effects on T cells, suggesting non-glycan-mediated recognition pathways.

Conclusions:

  • Candida albicans recognition by intestinal epithelial cells and T cells is multifaceted, involving both glycan-dependent and independent mechanisms.
  • The distinct morphologies of C. albicans influence host cell responses, potentially contributing to the inflammatory processes in IBD.
  • Further research is needed to fully understand the role of the intestinal mycobiome in IBD pathogenesis and host-microbe interactions.

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