Mechanisms of microbe-immune system dialogue within the skin

Abstract

The prevalence and severity of dermatological conditions such as atopic dermatitis have increased dramatically during recent decades. Many of the factors associated with an altered risk of developing inflammatory skin disorders have also been shown to alter the composition and diversity of non-pathogenic microbial communities that inhabit the human host. While the most densely microbial populated organ is the gut, culture and non-culture-based technologies have revealed a dynamic community of bacteria, fungi, viruses and mites that exist on healthy human skin, which change during disease. In this review, we highlight some of the recent findings on the mechanisms through which microbes interact with each other on the skin and the signalling systems that mediate communication between the immune system and skin-associated microbes. In addition, we summarize the ongoing clinical studies that are targeting the microbiome in patients with skin disorders. While significant efforts are still required to decipher the mechanisms underpinning host-microbe communication relevant to skin health, it is likely that disease-related microbial communities, or Dermatypes, will help identify personalized treatments and appropriate microbial reconstitution strategies.

Fig. 1. Microbe–microbe and microbe–host interactions on the skin.

Diverse microbes on the skin surface and hair follicles interact with each other such that they limit the proliferation of pathogenic organisms. Microbes influence the growth of other microbes via secretion of bacteriocins, auto-induced peptides (AIPs), phenol soluble modulins (PSMs) and cyclic anti-microbial peptides (AMPs). Keratinocytes inhibit microbial growth by constitutively secreting antimicrobial peptides such as cathelicidin and human beta defensins (hβDs). Pattern recognition receptors (PRRs) recognize microbial structures to induce appropriate innate immune responses. Lipotechoic acid (LTA) from Staphylococcus (S.) epidermidis is recognized via toll-like receptor 2 (TLR-2). Mucosa-associated invariant T (MAIT) cells specifically respond to microbial-derived riboflavin metabolites. Innate cells such as Langerhans cells (LCs) and dendritic cells (DCs) sample microbial antigens within the hair follicle, while secretion of chemokines including chemokine (C-C motif) ligand 20 (CCL20) control the recruitment of lymphocyte subsets. Dysbiosis is associated with overgrowth of microbes such as S. aureus, which employs clumping factor B (ClfB), toxins, proteases and superantigens to colonize the skin and induce damaging inflammatory responses. Figure created with BioRender.com.