The First Sign of Defense

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Science  18 Jan 2008:
Vol. 319, Issue 5861, pp. 259
DOI: 10.1126/science.319.5861.259b

Soon after birth, the intestine is exposed to multiple bacterial species, as its colonization by microflora begins. Some of the new immigrants are pathogenic, yet it is not clear how early innate immune protection and the initial maintenance of the normal microbiota are achieved. In particular, the antimicrobial peptide-producing Paneth cells only develop some time after the initial neonatal period, raising the possibility that the neonatal intestine may harbor another means of defense.

In support of this, Ménard et al. observed that although established enteric antimicrobial peptides were absent from the neonatal intestinal epithelium, they increased over time. In contrast, expression of the active, processed form of the cathelicidin cathelin-related antimicrobial peptide (CRAMP) was prominent specifically in the early stages of development in the epithelium of the small intestine. This peptide showed significant activity against a bacterial pathogen, as well as against commensal bacteria, and its importance for neonatal protection was confirmed using infection of mice deficient in CRAMP. Expression of the peptide diminished postnatally, corresponding with a gradual proliferative replacement of the epithelia, rather than with a down-regulation of transcriptional activity. The results suggest that the newborn intestine uses an ongoing developmental program to help establish control of microbial colonization and infection early on.— SJS

J. Exp. Med. 205, 10.1084/jem.20071022 (2008).

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