Differentiation of keratinocytes or exposure to type 2 cytokines diminishes S. aureus internalization

• Published in: mSphere Vol. 9; no. 4; p. e0068523
• Main Authors: Morgenstern, Alexis R, Peterson, Liam F, Arnold, Kimberly A, Brewer, Matthew G
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 23-04-2024
• Subjects: Antibiotics; Atopic dermatitis; Bacteria; bacterial invasion; Bullous pemphigoid; Cytokines; Genomes; Host-Microbial Interactions; Immune response; inflammation; Interleukin 13; Interleukin 4; Internalization; keratinocyte; Keratinocytes; Psoriasis; Research Article; S. aureus; Skin diseases; Staphylococcus aureus; Staphylococcus infections; S. aureus; inflammation; keratinocyte; bacterial invasion
• ISSN: 2379-5042; 2379-5042
• DOI: 10.1128/msphere.00685-23

is a leading cause of skin and soft tissue infections. Colonization by this bacterium is increased in individuals with chronic cutaneous diseases such as atopic dermatitis, psoriasis, and bullous pemphigoid. The greater abundance of
on the skin of subjects with atopic dermatitis in particular has been linked to recurrent cutaneous infections. The primary cell type of the epidermal layer of the skin is the keratinocyte, and it is thought that
internalized in keratinocytes associates with an increased incidence of skin infections. This study addresses whether keratinocyte differentiation and/or inflammation, two important characteristics altered in cutaneous diseases, influence bacterial internalization. To do this,
internalization was measured in immortalized and primary keratinocytes that were differentiated using high Ca
-containing media and/or exposed to cytokines characteristic of atopic dermatitis (IL-4 and IL-13) or psoriasis (IL-17A and IL-22) skin. Our results indicate that
internalization is uniquely decreased upon keratinocyte differentiation, since this was not observed with another skin-resident bacterium,
. Additionally, treatment with IL-4 + IL-13 diminished bacterial internalization. We interpret this decrease as a mechanism of keratinocyte-based bacterial killing since a similar number of bacterial genomes were detected in cytokine-treated cells, but less viable internalized
was recovered. Finally, of the receptors reported for
binding/internalizing into keratinocytes, expression of the α
component of the α
β
integrin was in greatest accordance with the number of internalized bacteria in the context of keratinocyte differentiation.IMPORTANCEIndividuals with chronic cutaneous diseases demonstrate heightened susceptibility for severe and recurrent infections from
. What drives this altered susceptibility remains poorly understood. Previous publications have detected
as deep as the dermal layer of skin in subjects with atopic dermatitis, suggesting that the cutaneous environment of this disease enables deeper bacterial infiltration than occurs in healthy individuals. This observation indicates that
has greater opportunity to interact with multiple skin cell types in individuals with chronic inflammatory skin diseases. Identifying the characteristics of the skin that influence bacterial internalization, a common method to establish reservoirs and evade the immune response, is critical for our understanding of
pathogenesis. The significance of this research is the novel identification of epidermal characteristics that influence
internalization. With this knowledge, methods can be developed to identify patient populations at greater risk for cutaneous infections.