Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice.
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.
Aberg
Karin M
KM
Dermatology and Medical (Metabolism) Services, Veterans Affairs Medical Center, and Department of Dermatology, UCSF, San Francisco, California 94121, USA.
Radek
Katherine A
KA
Choi
Eung-Ho
EH
Kim
Dong-Kun
DK
Demerjian
Marianne
M
Hupe
Melanie
M
Kerbleski
Joseph
J
Gallo
Richard L
RL
Ganz
Tomas
T
Mauro
Theodora
T
Feingold
Kenneth R
KR
Elias
Peter M
PM
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
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D005938:Glucocorticoids; D002990:Clobetasol