Candida albicans SC5314 inhibits NLRP3/NLRP6 inflammasome expression and dampens human intestinal barrier activity in Caco-2 cell monolayer model.
Mao. Xiaqiong X; Qiu. Xinyun X; Jiao. Chunhua C; Lu. Meijiao M; Zhao. Xiaojing X; Li. Xueting X; Li. Jiajia J; Ma. Jingjing J; Zhang. Hongjie H
Key Findings
- Live and heat‑killed Candida albicans both suppress NLRP3 and NLRP6 inflammasome components in intestinal cells.
- Candida infection leads to a significant drop in antimicrobial peptides, including LL‑37, BD‑2, and BD‑3.
- Tight‑junction proteins occludin and ZO‑1 are reduced, indicating a weakened intestinal barrier.
Practical Outcomes
- If you have gut Candida overgrowth, it may blunt your body's natural antimicrobial peptides like LL‑37 and compromise gut barrier integrity. Managing fungal load through diet, antifungal supplements, or probiotics could help preserve these defenses, though human studies are still needed to confirm the effect.
Summary
The study shows that the common gut fungus Candida albicans can lower the gut's natural defenses by reducing the production of the antimicrobial peptide LL-37 and weakening the tight‑junction proteins that keep the intestinal lining sealed, even when the fungus is dead.
Abstract
Candida albicans is an opportunistic fungal pathogen that colonizes human gastro-intestinal mucosal tissues. Its effect on the immune response in intestinal epithelial cells and on the intestinal mucosal barrier are not yet fully understood. In this study, we investigated Caco-2 cells, a monolayer model of intestinal epithelial cells, with or without treatment with C. albicans SC5314 (CA) or heat-inactivated CA (CA-inact). RNA sequencing was conducted, and the mRNA and protein levels of NOD-like receptor pyrin domain-containing protein 3 (NLRP3) or NLRP6/ASC/caspase-1 inflammasome signaling pathway components, inflammatory cytokines (interleukin-18 [IL-18] and IL-1β), anti-microbial peptides (AMPs; β-defensin-2 [BD-2], BD-3, and LL-37), and tight junction proteins (occludin and zona occludens-1 [ZO-1]) were examined by real-time PCR, western blotting, and/or immunofluorescence microscopy. Lactase dehydrogenase (LDH) activity in the Caco-2 cell supernatant were measured by enzyme kinetics analysis. Our results showed that the NOD-like receptor signaling pathway participates in the CA- and CA-inact-infected Caco-2 cells, as shown by microarray analysis of total mRNA expression. The expression of NLRP3, NLRP6, ASC, BD-2, BD-3, occludin, and ZO-1 were significantly decreased in Caco-2 cells infected with CA and CA-inact compared to that in the untreated control. IL-1β expression was decreased in the Caco-2 cells in both the CA- and CA-inact-infected groups compared to that in the control. Caspase-1 and IL-18 levels were not markedly affected by CA or CA-inact in Caco-2 cells. Our findings indicate that CA can inhibit the NLRP3 and NLRP6 pathways and dampen human intestinal mucosal barrier activity by decreasing the production of AMPs and tight junction proteins, independent of CA activity.
Study Information
pubmed
2019
2019-10-16T00:00:00.000Z
10.1016/j.cyto.2019.154882
24
30