Novel mechanisms of microbial crosstalk with skin innate immunity

Abstract

Skin is one of the largest organs of the body and protects the host from direct exposure to its environment. 1 Anatomically, the skin is composed of three major compartments: an outermost epidermis, an intermediate dermis and an innermost hypodermis. The skin protects the host from all depth of skin injury including puncture wounds. Thus, all depths of the skin are poised to respond to both external injury and infection. The epidermal layer of the skin consists of keratinocytes, Langerhans cells (LCs), corneocytes and melanocytes. Keratinocytes are the most abundant cell type of the epidermis. They can detect pathogens and initiate an immune response by activating immune cells through the secretion of cytokines.Keratinocytes also differentiate into corneocytes that form a denucleated and somewhat inert outer layer, rich in keratin filaments and surrounded by intercellular lipids. Together these components separate the body from the external environment and prevent water and heat loss. 2 The epidermis also consists of invaginations into the dermis, comprising the stem cell niche, the hair follicle, and the sebaceous gland-collectively termed the pilosebaceous unit. LCs are also present in the epidermis. LCs are specialized dendritic cells that sample the external environment and serve as the chief antigen presenting cells in the skin. 3 Recent studies now show that keratinocytes can also sample the environment and act as antigen presenting cells. 4 Commensal microbes induce the expression of major histocompatibility complex (MHC) class II expression in keratinocytes

Sarecycline inhibits protein translation inCutibacterium acnes70S ribosome using a two-site mechanism

“…C. acnes is a lipophilic bacterium, which together with other Propionibacterium species dominates in sebaceous sites. There it coexists with the commensal clades of Staphylococcus , such as S. epidermidis and S. hominis , and Corynebacterium ( 2 , 76 ). We demonstrated that bS22 and bL37 may penetrate the bacterial cell wall and inhibit protein synthesis, which leads us to suggest that they can work as bacteriocins, maintaining homeostasis of the skin microbiome and protecting the C. acnes niche.…”

Are Antimicrobial Peptides a 21st-Century Solution for Atopic Dermatitis?

“…Outermost barrier, immune function, protection from oxidative and mechanical stress [4,5] When one considers the skin complexity a compound's biological activity will be mainly influenced by two layers, the epidermis followed by the dermis. The reason for this is that, within these layers, all physical and chemical resistance to compound penetration, immunological response to outside factors, and the management of microbial colonization and infection resistance is provided [3,4]. When alterations to these layers occur, there is a window for the appearance of abnormal conditions within the skin and the development of hard-to-treat-and-manage diseases, such as AD.…”