Neonatal skin in mice and humans expresses increased levels of antimicrobial peptides: innate immunity during development of the adaptive response.
The expression of antimicrobial peptides and proteins is an important innate immune defense mechanism that has recently been shown to be essential for cutaneous defense against invasive bacterial disease. Newborns have an immature cellular immune defense system that leads to increased susceptibility to infections. Here we show that skin from embryonic and newborn mice, as well as human newborn foreskin, express antimicrobial peptides of the cathelicidin and beta-defensin gene families. Immunohistochemistry and in situ hybridization demonstrated abundant cathelicidin protein and mRNA is present in normal skin during the perinatal period. Quantitative real-time PCR showed mouse cathelicidin expression (CRAMP) is 10- to 100-fold greater in the perinatal period than adult. Murine beta-defensins-1 and -4 and human beta-defensin-2 were also present in newborn skin. Combined, human cathelicidin (LL-37/hCAP/18) and beta-defensin-2 demonstrated synergistic antimicrobial activity and efficiently killed group B Streptococcus, an important neonatal pathogen. Antimicrobial peptides may therefore provide a compensatory innate defense mechanism during development of cellular immune response mechanisms in the newborn period.
Dorschner
Robert A
RA
Division of Dermatology, Department of Medicine and Pediatrics, University of California, San Diego, USA.
Lin
Kenneth H
KH
Murakami
Masamoto
M
Gallo
Richard L
RL
D000222:Adaptation, Physiological / Q000276:immunology*; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D054804:Cathelicidins; D004357:Drug Synergism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000196:embryology / Q000254:growth & development; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000196:embryology / Q000254:growth & development* / Q000276:immunology*; D013292:Streptococcus agalactiae / Q000187:drug effects; D023083:beta-Defensins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology
D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; C406407:DEFB1 protein, human; C106641:DEFB4A protein, human; D012333:RNA, Messenger; D023083:beta-Defensins