Potent and broad-spectrum antimicrobial activity of CXCL14 suggests an immediate role in skin infections.
The skin is constantly exposed to commensal microflora and pathogenic microbes. The stratum corneum of the outermost skin layer employs distinct tools such as harsh growth conditions and numerous antimicrobial peptides (AMPs) to discriminate between beneficial cutaneous microflora and harmful bacteria. How the skin deals with microbes that have gained access to the live part of the skin as a result of microinjuries is ill defined. In this study, we report that the chemokine CXCL14 is a broad-spectrum AMP with killing activity for cutaneous gram-positive bacteria and Candida albicans as well as the gram-negative enterobacterium Escherichia coli. Based on two separate bacteria-killing assays, CXCL14 compares favorably with other tested AMPs, including human beta-defensin and the chemokine CCL20. Increased salt concentrations and skin-typical pH conditions did not abrogate its AMP function. This novel AMP is highly abundant in the epidermis and dermis of healthy human skin but is down-modulated under conditions of inflammation and disease. We propose that CXCL14 fights bacteria at the earliest stage of infection, well before the establishment of inflammation, and thus fulfills a unique role in antimicrobial immunity.
Maerki
Christa
C
Theodor Kocher Institute, University of Bern, Bern, Switzerland.
Meuter
Simone
S
Liebi
Mark
M
Mühlemann
Kathrin
K
Frederick
Mitchell J
MJ
Yawalkar
Nikhil
N
Moser
Bernhard
B
Wolf
Marlene
M
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000302:isolation & purification / Q000502:physiology*; D002177:Candidiasis / Q000276:immunology / Q000382:microbiology / Q000628:therapy; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002474:Cell-Free System / Q000276:immunology / Q000382:microbiology; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D016905:Gram-Negative Bacterial Infections / Q000276:immunology / Q000382:microbiology / Q000628:therapy; D016908:Gram-Positive Bacterial Infections / Q000276:immunology / Q000382:microbiology / Q000628:therapy; D006801:Humans; D018836:Inflammation Mediators / Q000302:isolation & purification / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D012874:Skin Diseases, Infectious / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000628:therapy*
D023181:Antimicrobial Cationic Peptides; C118056:CXCL14 protein, human; D019743:Chemokines, CXC; D018836:Inflammation Mediators