# MUC16-dependent Renal Vascular Adhesion of Candida Promotes Tissue Invasion and Predicts Clinical Outcome in Candidemia

## TL;DR

This study shows that the protein MUC16 helps Candida stick to blood vessels in the kidneys, leading to infection and worse outcomes in patients.

## Contribution

The study identifies MUC16 as a key host factor mediating Candida vascular adhesion and tissue invasion through a ternary complex with Als3p and N-cadherin.

## Key findings

- MUC16 deletion in mice reduced fungal vascular binding and neutrophil recruitment.
- MUC16 expression is induced via MINCLE-, TLR9-, and Dectin-1–dependent signaling.
- A MUC16 T10155I variant and elevated MUC16 levels correlate with higher 30-day mortality in candidemia.

## Abstract

Bloodstream infection with Candida species is associated with high mortality, yet the molecular basis of vascular adhesion and invasion remains unclear. We identify the endothelial surface mucin MUC16 as a key host factor enabling fungal vascular adherence. The MUC16 SEA domain directly engages the Candida adhesin Als3p and endothelial N-cadherin to form a ternary complex that promotes endothelial attachment and vascular invasion. Genetic deletion of Muc16 in mice markedly reduced fungal vascular binding, renal fungal burden, and Ly6Ghi CD11b+ neutrophil recruitment following intravenous infection, and diminished oral colonization in an oral model. Inflammatory induction of MUC16 occurred via MINCLE-, TLR9-, and Dectin-1–dependent signaling, converging on CARD9. In clinical cohorts, a MUC16 T10155I variant and elevated circulating MUC16 were associated with increased 30-day mortality. These findings establish MUC16 as a mechanistic link between endothelial sensing and Candida vascular invasion, with prognostic relevance in candidemia.