Host Immunity to Malassezia in Health and Disease

Abstract

The microbiota plays an integral role in shaping physical and functional aspects of the skin. While a healthy microbiota contributes to the maintenance of immune homeostasis, dysbiosis can result in the development of diverse skin pathologies. This dichotomous feature of the skin microbiota holds true not only for bacteria, but also for fungi that colonize the skin. As such, the yeast Malassezia, which is by far the most abundant component of the skin mycobiota, is associated with a variety of skin disorders, of which some can be chronic and severe and have a significant impact on the quality of life of those affected. Understanding the causative relationship between Malassezia and the development of such skin disorders requires in-depth knowledge of the mechanism by which the immune system interacts with and responds to the fungus. In this review, we will discuss recent advances in our understanding of the immune response to Malassezia and how the implicated cells and cytokine pathways prevent uncontrolled fungal growth to maintain commensalism in the mammalian skin. We also review how the antifungal response is currently thought to affect the development and severity of inflammatory disorders of the skin and at distant sites.

Prevalence of Malassezia species on the skin of HIV-seropositive patients

“…AhR‐mediated signaling is appreciated as a major player in the physiology and pathology of the human skin which influences, for example, the skin’s responses to environmental toxins (i.e. dioxins) and bacterial stimuli 20 . Malassezia -derived metabolites, in particular indoles, can trigger AhR signaling, the activation of which can regulate skin homeostasis in manifold ways, including oxidation, epidermal barrier function, melanogenesis, and innate immunity⁠.…”

“…Importantly, AhR has been implicated in type 17 immunity as it promotes Th17 differentiation and stimulates the production of IL-17A and related cytokines by Th17 cells and innate lymphoid cells (ILCs) 21 . IL-17 cytokines prevent the overgrowth of Malassezia on the murine skin 20 . A similar activity was described for IL-17 against other fungi, in particular Candida albicans , on the skin and mucosal surfaces 22 .…”

“…A similar activity was described for IL-17 against other fungi, in particular Candida albicans , on the skin and mucosal surfaces 22 . However, no case has been reported with a genetic defect in the IL-17 signaling pathway manifesting as detectable overgrowth of Malassezia or leading to the development of Malassezia -associated skin disorders 20 .…”

“…However, the underlying cause and the Card9-independent regulatory mechanisms of Malassezia are unclear so far 24 . Other classes of receptors, particularly those relevant to keratinocytes, which lack Syk/Card9-coupled C-type lectin receptors, are also implicated in the detection of Malassezia on the skin 20 .…”

In Vitro or In Vivo Models, the Next Frontier for Unraveling Interactions between Malassezia spp. and Hosts. How Much Do We Know?

“…They were proposed to modulate the immune response through different mechanisms. For example, the composition of the cell wall contributes to the evasion of phagocytosis and a decrease in the release of proinflammatory cytokines by immune cells (IL-1β, IL-6 and TNF-α) [ 14 ], and the induction of IL-17 that leads to skin inflammation [ 15 , 16 ] and the indolic compounds that may inhibit the respiratory burst of neutrophils [ 17 , 18 , 19 , 20 , 21 ]. Furthermore, nutritional requirements may lead to the release of fatty acids that can contribute to skin irritation [ 10 ].…”