title: 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 beta-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.affiliation: Dermatology and Medical (Metabolism) Services, Veterans Affairs Medical Center, and Department of Dermatology, UCSF, San Francisco, California 94121, USA.
authors.forename: Karin M
authors.initials: KM
authors.lastname: Aberg
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Radek
authors.forename: Eung-Ho
authors.initials: EH
authors.lastname: Choi
authors.forename: Dong-Kun
authors.initials: DK
authors.lastname: Kim
authors.forename: Marianne
authors.initials: M
authors.lastname: Demerjian
authors.forename: Melanie
authors.initials: M
authors.lastname: Hupe
authors.forename: Joseph
authors.initials: J
authors.lastname: Kerbleski
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
authors.forename: Tomas
authors.initials: T
authors.lastname: Ganz
authors.forename: Theodora
authors.initials: T
authors.lastname: Mauro
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Feingold
authors.forename: Peter M
authors.initials: PM
authors.lastname: Elias
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D002990:Clobetasol / Q000008:administration & dosage / Q000378:metabolism; D004198:Disease Susceptibility; D015536:Down-Regulation; D004817:Epidermis / Q000737:chemistry / Q000378:metabolism* / Q000382:microbiology; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D051379:Mice; D008819:Mice, Nude; D012874:Skin Diseases, Infectious / Q000378:metabolism* / Q000473:pathology; D013290:Streptococcal Infections / Q000378:metabolism* / Q000473:pathology; D013297:Streptococcus pyogenes; D013315:Stress, Psychological
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D005938:Glucocorticoids; D002990:Clobetasol