Keratinocytes as sensors and central players in the immune defense against Staphylococcus aureus in the skin

Abstract

Healthy human skin provides an effective mechanical as well as immunologic barrier against pathogenic microorganisms with keratinocytes as the main cell type in the epidermis actively participating and orchestrating the innate immune response of the skin. As constituent of the outermost layer encountering potential pathogens they have to sense signals from the environment and must be able to initiate a differential immune response to harmless commensals and harmful pathogens. Staphylococci are among the most abundant colonizers of the skin: Whereas Staphylococcus epidermidis is part of the skin microbiota and ubiquitously colonizes human skin, Staphylococcus aureus is only rarely found on healthy human skin, but frequently colonizes the skin of atopic dermatitis (AD) patients. This review highlights recent advances in understanding how keratinocytes as sessile innate immune cells orchestrate an effective defense against S. aureus in healthy skin and the mechanisms leading to an impaired keratinocyte function in AD patients.

A Phage Lysin Fused to a Cell-Penetrating Peptide Kills Intracellular Methicillin-Resistant Staphylococcus aureus in Keratinocytes and Has Potential as a Treatment for Skin Infections in Mice

“…S. aureus is the major cause of SSSIs and has the ability to invade and survive in distinctly differentiated keratinocytes (1,3). However, the intracellular persistence of the bacteria in SSSIs contributes to the difficulty of antibiotic treatment, especially in MRSA infections (30,31).…”

“…H ealthy skin provides a unique ecological environment and immunological barrier against pathogenic microorganisms, especially Staphylococcus aureus, which is the main cause of skin and skin structure infections (SSSIs) (1,2). Keratinocytes are the major cell type in the epidermis and actively participate in and orchestrate the innate immune response of the skin (3). Recent studies have illuminated that, like immune cells, keratinocytes are initial sensors for skin and important producers of antimicrobial peptides and proinflammatory cytokines at the preliminary stage of an S. aureus infection (4)(5)(6).…”

NLRP10 Affects the Stability of Abin-1 To Control Inflammatory Responses

“…By contrast, inflammasomeindependent pro-and anti-inflammatory roles of NLRP10 in Shigella flexneri and Leishmania major infection were also described (18,19), combined with work suggesting a role of NLRP10 in enhancing T cell responses by increasing IL-12 production by dendritic cells (20). NLRP10 is highly expressed in the epidermis of the skin, where keratinocytes express several pattern recognition receptors important for host defense against bacterial, viral, and fungal pathogens (18,(21)(22)(23). Genome-wide association studies suggest a link between NLRP10 and allergic and inflammatory pathways in atopic dermatitis, food allergies, and contact hypersensitivity.…”

In vivo Anti-inflammatory Activity of Lipidated Peptidomimetics Pam-(Lys-βNspe)6-NH2 and Lau-(Lys-βNspe)6-NH2 Against PMA-Induced Acute Inflammation

“…The detailed functions of FPR2 in skin inflammation have not been well-characterized to date. Activation of FPR2 by PSMα peptides leads to cytokine release, neutrophil chemotaxis and activation during Staphylococcus aureus skin infections ( 51 – 53 ). In sterile skin wounds, mouse Fpr1 and Fpr2 have been reported to mediate early neutrophil infiltration into the dermis prior to the production of neutrophil-specific chemokines such as CXCL-1 and CXCL-2 through recognition of FPR ligands produced at the site of injury ( 54 ).…”