Research – Innate antimicrobial immunity in the skin: A protective barrier against bacteria, viruses, and fungi


The epidermis, the outermost layer of the skin, is a physical barrier against pathogens. However, breach of the skin barrier through wounding introduces a myriad of microbes to the site of injury. Upon disturbance of the epidermal barrier, the innate immune system and its effectors play a key role in protecting humans against cutaneous and systemic infection [1]. Major constituents of the innate immune system include phagocytic cells, such as macrophages, neutrophils, and dendritic cells, as well as innate leukocytes, such as natural killer (NK) cells, mast cells, basophils, and eosinophils. In addition, epidermal keratinocytes act as active innate immune cells. In response to sensing pathogen-associated molecular patterns (PAMPs) expressed by microbes and host danger molecules, innate immune receptors present on keratinocytes become activated, causing release of inflammatory cytokines and host antimicrobial molecules [2, 3].

Recognition of pathogens

The first step of any immune response is recognition of potential pathogens. Germline-encoded pattern recognition receptors (PRRs) recognize PAMPs present on microbes and damaged-associated molecular patterns (DAMPs) on host cells (Fig 1) [4]. The four primary groups of human PRRs are toll-like receptors (TLRs), nucleotide-binding oligomerization domain-like receptors (NLRs), retinoic acid-inducible gene 1 (RIG-I)-like helicase receptors (RLRs) and c-type lectin receptors (CLRs) [4]. Signaling through PRRs has long been known to be essential for activation of the innate immune response. For example, stimulation of TLR2 increases the immune response to pathogens and helps rescue the inflammatory response of immunosuppressed patients with sepsis [5]. Although PRRs are not as specific as immune effectors of the adaptive immune system, different PRRs have evolved to recognize different molecular patterns [6]. For example, TLR2, TLR6, and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) appear to play an important role in host defense against staphylococcal aureus, whereas TLRs 2, 3, 7, 8, and 9 have been found to be activated by many viruses, including members of the herpesviruses, papillomaviruses, and poxviruses [7, 8]. CLRs and TLRs 2, 4, and 9 are thought to be primary receptors involved in recognition of fungal pathogens such as Candida albicans, and there are reports of specific PRR deficiencies in patients with chronic mucocutaneous infections [9, 10].

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