Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice
Karin M. Aberg, … , Kenneth R. Feingold, Peter M. Elias
Karin M. Aberg, … , Kenneth R. Feingold, Peter M. Elias
Published November 1, 2007
Citation Information: J Clin Invest. 2007;117(11):3339-3349. https://doi.org/10.1172/JCI31726.
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Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice

Abstract

The skin is the first line of defense against microbial infection, and psychological stress (PS) has been shown to have adverse effects on cutaneous barrier function. Here we show that PS increased the severity of group A Streptococcus pyogenes (GAS) cutaneous skin infection in mice; this was accompanied by increased production of endogenous glucocorticoids (GCs), which inhibited epidermal lipid synthesis and decreased lamellar body (LB) secretion. LBs encapsulate antimicrobial peptides (AMPs), and PS or systemic or topical GC administration downregulated epidermal expression of murine AMPs cathelin-related AMP and β-defensin 3. Pharmacological blockade of the stress hormone corticotrophin-releasing factor or of peripheral GC action, as well as topical administration of physiologic lipids, normalized epidermal AMP levels and delivery to LBs and decreased the severity of GAS infection during PS. Our results show that PS decreases the levels of 2 key AMPs in the epidermis and their delivery into LBs and that this is attributable to increased endogenous GC production. These data suggest that GC blockade and/or topical lipid administration could normalize cutaneous antimicrobial defense during PS or GC increase. We believe this to be the first mechanistic link between PS and increased susceptibility to infection by microbial pathogens.

Authors

Karin M. Aberg, Katherine A. Radek, Eung-Ho Choi, Dong-Kun Kim, Marianne Demerjian, Melanie Hupe, Joseph Kerbleski, Richard L. Gallo, Tomas Ganz, Theodora Mauro, Kenneth R. Feingold, Peter M. Elias

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Figure 1

PS downregulates epidermal AMP expression.

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PS downregulates epidermal AMP expression. Normal hairless mice (n = 3 e...
Normal hairless mice (n = 3 each for immuno­histochemistry and RT-PCR studies; 3–4 replications for each experiment in these and subsequent experiments) were exposed to insomnia- and crowding-induced PS (B and E) for 72 h, while littermate controls (A and D) were not stressed. Frozen sections (8 μm) were stained with primary antibodies to CRAMP and mBD3 and processed as described in Methods (for controls, see Supplemental Figure 1). Throughout the figures, white arrows indicate normal levels of positive immunostaining (green); white arrowheads indicate reduced staining; asterisks indicate positive immunostaining of pilosebaceous follicles; and “d” and “e” indicate dermis and epidermis, respectively. (C and F) mRNA was extracted from PS and control mouse epidermis, followed by quantitative RT-PCR (see Methods). Normalization in this and all subsequent studies was to 18S mRNA, with 2–3 replicates per sample (n = 3 per cohort). Scale bars: 50 μm. *P = 0.007.