Skin Commensals Amplify the Innate Immune Response to Pathogens by Activation of Distinct Signaling Pathways

Abstract

Little is known about the impact of different microbial signals on skin barrier organ function and the interdependency between resident microflora and pathogenic microorganisms. This study shows that commensal and pathogenic staphylococci differ in their ability to induce expression of antimicrobial peptides/proteins (AMPs) and activate different signaling pathways in human primary keratinocytes. Whereas secreted factors of skin commensals induce expression of the AMPs HBD-3 and RNase7 in primary human keratinocytes via Toll-like receptor (TLR)-2, EGFR, and NF-κB activation, those of pathogenic staphylococci activate the mitogen-activated protein kinase and phosphatidylinositol 3-kinase/AKT signaling pathways and suppress NF-κB activation. Interestingly, commensal bacteria are able to amplify the innate immune response of human keratinocytes to pathogens by increased induction of AMP expression and abrogation of NF-κB suppression, suggesting that the two activation pathways can act in a synergistic way. These data indicate that commensal and pathogenic microorganisms evolved specific mechanisms to modulate innate immunity of the skin.

The Malassezia Genus in Skin and Systemic Diseases

“…Species like Staphylococcus epidermidis have the ability to amplify the innate immune response through an increase in the constitutive expression of antimicrobial peptides, which are, however, active against the pathogenic species Staphylococcus aureus (328). A delineation of comparable interaction mechanisms would contribute to a better understanding of the significance of the reported differential colonization of lesional skin by distinctive, "pathogenic" Malassezia species subtypes compared to "nonvirulent" ones associated with healthy skin.…”

Staphylococcus aureus skin colonization is promoted by barrier disruption and leads to local inflammation

“…UVB (290-320 nm) irradiation is known to be a major cause for the epidermal damage in human skin (3). Keratinocytes constitute for 90% of the cells found in the epidermis and are capable of producing cytokines in response to external stimuli (4). Human keratinocyte (HaCaT) cells were reported to be the appropriate experimented model to study the biological changes in human epidermis (5).…”

The Amino Acid Sequence of Neisseria lactamica PorB Surface-Exposed Loops Influences Toll-Like Receptor 2-Dependent Cell Activation

“…Regulation of TLR-dependent cell activation is a common mech-anism employed by several microorganisms to actively prevent or downregulate host cell responses that control local inflammation. For example, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Pseudomonas aeruginosa induce different amounts of the inflammatory mediators interleukin 8 (IL-8) and RANTES (55). An inverse correlation between serum levels of IL-8 and RANTES has also been shown in patients with meningococcal infections, where high levels of IL-8 and low levels of RANTES correlate with severe disease and poor prognosis (i.e., acute bacterial meningitis and meningococcal septic shock) while low IL-8 and high RANTES levels correlate with mild systemic meningitis and are associated with survival (15).…”