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^a Department of Medicine, University of Wales, College of Medicine, Heath Park, Cardiff CF4 4XX, United Kingdom
^b Department of Medical Biochemistry, University of Wales, College of Medicine, Heath Park, Cardiff CF4 4XX, United Kingdom
^c Nestlé Research Center, Vers-Chez-Les-Blanc, CH-1000 Lausanne 26, Switzerland
^d Sanofi-Synthelabo, 31676 Labège Cedex, France
Nestlé Research Center, Vers-Chez-Les-Blanc, CH 1000 Lausanne 26, Switzerland.41-21-785-892541-21-785-8671

eduardo.schiffrin{at}rdls.nestle.com

Little is known about innate immunity to bacteria after birth in the hitherto sterile fetal intestine. Breast-feeding has long been associated with a lower incidence of gastrointestinal infections and inflammatory and allergic diseases. We found in human breast milk a 48-kD polypeptide, which we confirmed by mass spectrometry and sequencing to be a soluble form of the bacterial pattern recognition receptor CD14 (sCD14). Milk sCD14 (m-sCD14) concentrations were up to 20-fold higher than serum sCD14 from nonpregnant, pregnant, or lactating women. In contrast, lipopolysaccharide (LPS)-binding protein was at very low levels. Mammary epithelial cells produced 48-kD sCD14. m-sCD14 mediated activation by LPS and whole bacteria of CD14 negative cells, including intestinal epithelial cells, resulting in release of innate immune response molecules. m-sCD14 was undetectable in the infant formulas and commercial (cows') milk tested, although it was present in bovine colostrum. These findings indicate a sentinel role for sCD14 in human milk during bacterial colonization of the gut, and suggest that m-sCD14 may be involved in modulating local innate and adaptive immune responses, thus controlling homeostasis in the neonatal intestine.

Key Words: innate immunity • neonatal immunity • mucosal immunity • intestinal immune response • breast-feeding

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