Antimicrobial and antiviral signaling in the skin.

* Skin injury allows pathogenic bacteria and viruses to penetrate the epidermis. PAMPs and DAMPs are recognized by TLRs, which induce the projection of pro-inflammatory cytokines by dendritic cells. Examples of pro-inflammatory cytokines include IL-1β, TNFα, and IFNγ. Inflammatory cytokines recruit neutrophils and macrophages to the site of injury and promote production of AMPs by these inflammatory cells and also by keratinocytes. The AMPs produced include cathelicidins (LL-37) and defensins (hBD2). Some TLRs, such as TLR3, recognize viral components. IL-27 is produced in response to TLR3 activation and induces translation of anti-viral ISGs, such as OAS2, by keratinocytes. AMPs and ISGs are important effector molecules for pathogen defense and skin healing. Commensal bacteria, such as Staphylococcus epidermidis, promote AMP production. Pathogenic bacteria, such as S. aureus, inhibit the production of AMPs; pathogenic viruses, such as HSV, inhibit ISG production. *Created with BioRender. AMP, antimicrobial protein; DAMP, damage-associated molecular pattern; hBD2, human β-defensin-2; HSV, herpes simplex virus; IL, interleukin; IFN, interferon; ISG, interferon-stimulated gene; OAS, oligoadenylate synthetase; PAMP, pathogen-associated molecular pattern; TLR, toll-like receptor; TNF, tumor necrosis factor.