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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Research Article

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 8

PS increases the severity of cutaneous GAS infection.

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PS increases the severity of cutaneous GAS infection. (A) Female 8- to 1...
(A) Female 8- to 10-wk-old Skh1/Hr mice were subjected to normal conditions or PS for 72 h, and then subsequently injected intradermally with 4.8 x 108 CFU/ml GAS (n = 6 per group). Mice were then photographed daily for 4 d to monitor lesion size. (A) Representative lesions at day 4 from nonstressed and PS mice. (B) Lesion size (mean ± SEM) was calculated ± SEM for day 1 and day 4 lesions. *P < 0.05 versus nonstressed. (C) Representative lesions of PS mice (n = 5–6 per group) immediately prior to and 72 h after IP injection with either vehicle or RU-486 (6 mg/kg). After 72 h of PS or nonstressed conditions, mice were injected intradermally with 4.8 x 108 CFU/ml GAS. A representative photograph of day 4 lesions from each group is shown. (D) Lesion size (mean ± SEM) was calculated for day 4 lesions. †P < 0.05 versus PS and RU-486; #P < 0.05 versus PS and vehicle.