Role of Mannose‐Binding Lectin in the Innate Defense againstCandida albicans:Enhancement of Complement Activation, but Lack of Opsonic Function, in Phagocytosis by Human Dendritic Cells

Abstract

Mannose-binding lectin (MBL) is a serum collectin believed to be of importance in innate immunity. We have investigated the role of MBL in the first-line defense against Candida albicans, an opportunistic fungal pathogen. MBL bound C. albicans via its lectin domain, resulting in agglutination of the organisms upon their outgrowth of hyphae. In a human in vitro MBL system, deposition of C4 fragments on C. albicans was increased when exogenous MBL was added to serum samples from MBL-deficient individuals. Similar enhancement of deposition of iC3b also was observed. MBL and enhanced opsonic C3 fragments mediated by MBL did not facilitate opsonophagocytosis of the organisms by monocyte-derived dendritic cells (DCs). However, MBL was found to inhibit the growth of C. albicans independently of complement activation, although, with complement activation, further inhibition was observed. We concluded that MBL plays an important role in the first-line defense against C. albicans without the need for opsonophagocytosis by DCs, in which a direct interaction of MBL with C. albicans results in agglutination and accelerated complement activation via the lectin pathway, leading to inhibition of growth.

Beta-Mannosyl Linkages Negatively Regulate Anaphylaxis and Vasculitis in Mice, Induced by CAWS, Fungal PAMPs Composed of Mannoprotein-Beta-Glucan Complex Secreted by Candida albicans

“…27) Neth et al analyzed the concentration of MBL in various inbred strains and found that all of the strains tested contained MBL.…”

“…Several reports indicated that Candida albicans could bind to MBL. 27,28) We have shown that CAWS-induced arteritis and anaphylactoid reaction is dependent on strains of mice. In the present study, we demonstrated the essential structure to induce arteritis and anaphylactoid reaction.…”

Fungal killing by mammalian phagocytic cells

“…MBL binds mannans in the cell walls of C. albicans both in vitro and in vivo [24], leading to complement deposition via the lectin pathway and subsequent phagocytosis [24,25]. In contrast, MBL binding to Blastomyces dermatitidis masks 1,3-beta-glucan recognition by macrophages, hindering the secretion of TNF-α [26].…”

Association of lectin pathway proteins with intra-abdominal Candida infection in high-risk surgical intensive-care unit patients. A prospective cohort study within the fungal infection network of Switzerland

“…MBL has been shown to bind to Candida albicans augmenting complement activation (14) and facilitating phagocytosis (15) (20,21), data are lacking with regard to Candida infections.…”