Developmental switch of intestinal antimicrobial peptide expression.
Paneth cell-derived enteric antimicrobial peptides provide protection from intestinal infection and maintenance of enteric homeostasis. Paneth cells, however, evolve only after the neonatal period, and the antimicrobial mechanisms that protect the newborn intestine are ill defined. Using quantitative reverse transcription-polymerase chain reaction, immunohistology, reverse-phase high-performance liquid chromatography, and mass spectrometry, we analyzed the antimicrobial repertoire in intestinal epithelial cells during postnatal development. Surprisingly, constitutive expression of the cathelin-related antimicrobial peptide (CRAMP) was observed, and the processed, antimicrobially active form was identified in neonatal epithelium. Peptide synthesis was limited to the first two weeks after birth and gradually disappeared with the onset of increased stem cell proliferation and epithelial cell migration along the crypt-villus axis. CRAMP conferred significant protection from intestinal bacterial growth of the newborn enteric pathogen Listeria monocytogenes. Thus, we describe the first example of a complete developmental switch in innate immune effector expression and anatomical distribution. Epithelial CRAMP expression might contribute to bacterial colonization and the establishment of gut homeostasis, and provide protection from enteric infection during the postnatal period.
Ménard
Sandrine
S
Swedish Institute for Infectious Disease Control, Karolinska Institute, 171 77 Stockholm, Sweden.
Förster
Valentina
V
Lotz
Michael
M
Gütle
Dominique
D
Duerr
Claudia U
CU
Gallo
Richard L
RL
Henriques-Normark
Birgitta
B
Pütsep
Katrin
K
Andersson
Mats
M
Glocker
Erik O
EO
Hornef
Mathias W
MW
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology*; D054804:Cathelicidins; D002465:Cell Movement; D049109:Cell Proliferation; D002851:Chromatography, High Pressure Liquid; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007413:Intestinal Mucosa / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins