Interaction of Candida Species with the Skin

Abstract

The human skin is commonly colonized by diverse fungal species. Some Candida species, especially C. albicans, do not only reside on the skin surface as commensals, but also cause infections by growing into the colonized tissue. However, defense mechanisms at the skin barrier level are very efficient, involving residential non-immune and immune cells as well as immune cells specifically recruited to the site of infection. Therefore, the skin is an effective barrier against fungal infection. While most studies about commensal and pathogenic interaction of Candida species with host epithelia focus on the interaction with mucosal surfaces such as the vaginal and gastrointestinal epithelia, less is known about the mechanisms underlying Candida interaction with the skin. In this review, we focus on the ecology and molecular pathogenesis of Candida species on the skin and give an overview of defense mechanisms against C. albicans in this context. We also discuss new research avenues in dermal infection, including the involvement of neurons, fibroblasts, and commensal bacteria in both mouse and human model systems.

Keywords: 3D-tissue models; Candida; fibroblasts; innate immunity; skin infection.

Figure 1

C. albicans interaction with the skin. In the commensal, noninvasive state, C. albicans exists in the yeast form on the tissue surface. Yeast cells can be detected through the dectin-1 receptor (Dec1) that is expressed by Langerhans cells in the epidermis. Activation of Langerhans cells (LCs) results in an interleukin-6 (IL-6)-dependent Th17 response, antimicrobial peptide production by keratinocytes and superficial antifungal defense. Commensal skin bacteria are also involved in preventing invasion of C. albicans into the skin by direct and indirect mechanisms. C. albicans invading the epidermis can moreover be detected by sensory neurons that promote IL-23 secretion by dermal dendritic cells and subsequent proliferation and IL-17 secretion of skin resident γδ T cells. Upon breaching of the epidermis, C. albicans is detected in the dermis by dermal dendritic cells which induce an IL-12-dependent Th1 response required for systemic immunity against the fungus. Dermal fibroblasts support direct antimicrobial defense in the dermis upon activation through TLR2 by C. albicans and IL-1β secretion and auto-activation. Secretion of IL-1β by dermal fibroblasts requires an additional yet unidentified signal from CD4⁺ T cells.