A Mannose-Binding Receptor is Expressed on Human Keratinocytes and Mediates Killing of Candida albicans

Abstract

Human keratinocytes are known to kill Candida albicans in vitro, but the mechanism of killing is not yet understood. Here, we demonstrate that spontaneous, ultraviolet-B-light-induced, alpha-melanocyte-stimulating-hormone-induced, and interleukin-8-induced Candida killing by keratinocytes can be inhibited with mannan and mannosylated bovine serum albumin (Man-BSA). A polyclonal goat serum raised against the human macrophage mannose receptor stained suprabasal keratinocytes, but no staining was observed on keratinocytes with a monoclonal antibody (mAb15) specific for the human macrophage mannose receptor. Mannose-affinity chromatography of keratinocyte extract isolated a 200 kDa protein, and on the Western blot the goat antiserum reacted with a 200 kDa protein. In radioligand binding studies, the binding of 125I-Man-BSA to human keratinocytes was inhibited by mannan in a concentration-dependent manner. Analysis of the binding revealed a single class keratinocyte mannose receptor with a KD of 1.4 x 10(-8) M and a Bmax of 1 x 10(4) binding sites per cell. The binding of 125I-Man- BSA to keratinocytes proved to be time-dependent, acid-precipitable, and Ca2+- and trypsin-sensitive. After trypsinization the receptors underwent a rapid recovery at 37 degrees C. These results demonstrate the presence of mannose receptor on human keratinocytes, and its active involvement in the killing of Candida albicans.

Neonatal Innate Immunity to Infectious Agents

“…Remarkably, the production of TNF-␣ was significantly greater when macrophages were exposed to S. cerevisiae than to C. albicans. This observation is in concert with published data that ␤-glucan is buried within the cell wall of C. albicans and that Candida uptake by macrophages and keratinocytes can be inhibited by mannan and, to a lower extent, by glucan (37,54,90). It is also possible that S. cerevisiae may have a higher density of ␤-glucan exposed on its surface compared to that of C. albicans.…”

“…B cell knockout mice, which lack functional antibodies, are as resistant to mucosal or invasive candidiasis of endogen origin as are immunocompetent controls (97). In addition, patients with X-linked agammaglobulinemia or severe hypogammaglobulinemia do not exhibit an increased susceptibility to either mucocutaneous or invasive candidal infections (52 (19,25,54,90). Recognition and uptake of Candida yeasts involve the macrophage MR, which is a type I membrane protein with three types of domains in the extracellular region (19,54,59,93).…”

Predicting the optimal geometry of microneedles and their array for dermal vaccination using a computational model

“…Our previous study revealed that the rate constants had little effect on the output of the model and can therefore be taken from general values from the literature (Römgens et al 2016). The initial receptor concentration was estimated from the cell density (6.2 × 10 4 cells/mm 3 for the dermis, 1.3 × 10 6 cells/mm 3 for the epidermis) and the number of receptors per cell (1 × 10 5 ) for both the epidermis and dermis (Avraméas et al 1996;McLellan et al 1998;Szolnoky et al 2001;Mulholland et al 2006;Römgens et al 2016). The diffusion coefficient in both these layers was based on measurements with 40 kDa dextran (Römgens et al 2015).…”

“…the default values for the rate constants, initial receptor concentrations, dose per microneedle, and diffusion coefficients are presented. these were based on values reported in the literature (avraméas et al 1996;mclellan et al 1998;szolnoky et al 2001;metz et al 2003;mulholland et al 2006;ibrahim et al 2012;römgens et al 2015;Vainshtein et al 2015). these values were used in all simulations unless stated otherwise.…”

The Evolving View of IL-17-Mediated Immunity in Defense Against Mucocutaneous Candidiasis in Humans

“…The macrophage MR, one of the best characterized C-type lectin receptor (CLR) was the first membrane receptor implicated in the recognition of Candida yeasts by human macrophages [43,44,[51][52][53]. Monocyte-derived human macrophages (MDM) ingested and killed unopsonized Candida blastoconidia but both phagocytosis and killing of unopsonized yeasts were slower than those of serum-opsonized Candida [42].…”