Colonization and infection of the skin by S. aureus: immune system evasion and the response to cationic antimicrobial peptides

Abstract

Staphylococcus aureus (S. aureus) is a widespread cutaneous pathogen responsible for the great majority of bacterial skin infections in humans. The incidence of skin infections by S. aureus reflects in part the competition between host cutaneous immune defenses and S. aureus virulence factors. As part of the innate immune system in the skin, cationic antimicrobial peptides (CAMPs) such as the β-defensins and cathelicidin contribute to host cutaneous defense, which prevents harmful microorganisms, like S. aureus, from crossing epithelial barriers. Conversely, S. aureus utilizes evasive mechanisms against host defenses to promote its colonization and infection of the skin. In this review, we focus on host-pathogen interactions during colonization and infection of the skin by S. aureus and methicillin-resistant Staphylococcus aureus (MRSA). We will discuss the peptides (defensins, cathelicidins, RNase7, dermcidin) and other mediators (toll-like receptor, IL-1 and IL-17) that comprise the host defense against S. aureus skin infection, as well as the various mechanisms by which S. aureus evades host defenses. It is anticipated that greater understanding of these mechanisms will enable development of more sustainable antimicrobial compounds and new therapeutic approaches to the treatment of S. aureus skin infection and colonization.

Figure 1.

Toll-like receptor-mediated cutaneous immune response against S. aureus. Toll-like receptor 2 (TLR2) and nucleotide-binding oligomerization domain containing 2 (NOD2), which are expressed by keratinocytes, respectively recognize S. aureus lipopeptides/lipoteichoic acid and muramyl dipeptide. Both TLR2 and NOD2 signaling triggers the activation of nuclear factor-κB (NF-κB), which leads to the production of AMPs, cytokines, chemokines, adhesion molecules and granulopoesis factors, all of which contribute to the cutaneous host defense against S. aureus.

Figure 2.

IL-1- and IL-17-mediated cutaneous immune response against S. aureus. Infection of the skin by S. aureus leads to the production of IL-1α, IL-1β and IL-17, which in turn triggers activation of nuclear factor-κB (NF-κB). These signaling pathways lead to the production of AMPs, cytokines, chemokines, adhesion molecules and granulopoesis factors, which recruit neutrophils from the circulation to the site of S. aureus infection in the skin. The recruited neutrophils form an abscess that helps control and limit the spread of the infection, and is ultimately required for bacterial clearance. IL-1R1, interleukin-1 receptor 1; IL-17R, interleukin-17 receptor.

Figure 3.

Strategies by which S. aureus evades CAMPs. S. aureus counteracts CAMPs by secreting trapping molecules and proteases that inactivate CAMPs and by modifying the cell membrane hydrophobicity or net charge [108].