Microbial symbiosis with the innate immune defense system of the skin

Abstract

Skin protects itself against infection through a variety of mechanisms. Antimicrobial peptides (AMPs) are major contributors to cutaneous innate immunity, and this system, combined with the unique ionic, lipid, and physical barrier of the epidermis, is the first-line defense against invading pathogens. However, recent studies have revealed that our skin's innate immune system is not solely of human origin. Staphylococcus epidermidis, a major constituent of the normal microflora on healthy human skin, acts as a barrier against colonization of potentially pathogenic microbes and against overgrowth of already present opportunistic pathogens. Our resident commensal microbes produce their own AMPs, act to enhance the normal production of AMPs by keratinocytes, and are beneficial to maintaining inflammatory homeostasis by suppressing excess cytokine release after minor epidermal injury. These observations indicate that the normal human skin microflora protects skin by various modes of action, a conclusion supported by many lines of evidence associating diseases such as acne, atopic dermatitis, psoriasis, and rosacea with an imbalance of the microflora even in the absence of classical infection. This review highlights recent observations on the importance of innate immune systems and the relationship with the normal skin microflora to maintain healthy skin.

Figure 1. Molecular interactions of microbial symbiosis in skin innate immune systems

Factors produced by skin commensal bacteria modulate the skin immune system. (a) In a steady state, S. epidermidis, a major constituent of the normal microflora on healthy human skin, produce antimicrobial peptides, PSMδ and PSMγ, which act as a barrier against colonization of potentially pathogenic microbes. In addition, S. epidermidis secretes a small molecule which increases expression of defensins in murine skin or human keratinocytes through TLR2 signaling. (b) After skin injury, host RNA from damaged cells activates TLR3 in keratinocytes. If uncontrolled inflammation occurs this can result in delayed wound healing. Staphylococcal LTA inhibits excess inflammatory cytokine release from keratinocytes and inflammation through a TLR2-dependent mechanism. IFR, IFN-regulatory factor; JNK, C-Jun kinase; MyD88, Myeloid differentiation primary response gene 88; NF-kB, nuclear factor kappa-B; TRAF, TNF receptor-associated factor; TRIF, TIR-domain-containing adapter-inducing interferon-β.