The Macrophage Inducible C-type Lectin (Mincle) is a Receptor for the Yeast, Candida Albicans

Abstract

The Macrophage-Inducible C-type Lectin (Mincle) belongs to the family of C-type lectin receptors some of which have been well characterised. We investigated a role for Mincle in response to systemic candidiasis both in vivo and ex vivo. Our results show that while Mincle recognises C. albicans it is not phagocytic or candicidal. It does however, recognise this yeast as measured by reduced TNF-α production in Mincle deficient bone marrow-derived macrophages. Furthermore, there was a significant reduction in the cytokines KC, IL-1β, IL-10, IL-13, GCS-F, MIP-1β and RANTES in these cells. By using a mouse model of systemic infection, we were able to investigate levels of yeast fungal burden and tissue damage inMincle-/- and isogenic control mice. Mincle deficient mice were more susceptible to C. albicans infection, demonstrated by increased fungal burden and increased tissue damage in the kidney and brain of our knock-out mice, confirming a role for Mincle in control of C. albicans infection. Mincle shares some features in common with the β-glucan receptor (Dectin-1) and its close relative Dectin-2. Dectin-1 and Dectin-2 have both been shown to recognise the yeast Candida albicans. We therefore, went on to look at the RNA and protein expression profiles of these three C-type lectins and found Mincle was consistently upregulated in response to Candida in the brain, kidney, lung and spleen. Dectin-1 showed delayed induction and Dectin-2 was significantly up-regulated in all tissues in the absence of Mincle.