The Journal of Experimental Medicine
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Published online 15 May 2000.
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© The Rockefeller University Press, 0022-1007/2000/5/1807/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 10, May 15, 2000 1807-1812

Brief Definitive Report

Innate Recognition of Bacteria in Human Milk Is Mediated by a Milk-Derived Highly Expressed Pattern Recognition Receptor, Soluble Cd14

Mario O. Labétaa, Karine Vidalc, Julia E. Rey Noresa, Mauricio Ariasa, Natalio Vitad, B. Paul Morganb, Jean Claude Guillemotd, Denis Loyauxd, Pascual Ferrarad, Daniel Schmidc, Michael Affolterc, Leszek K. Borysiewicza, Anne Donnet-Hughesc, and Eduardo J. Schiffrinc

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

© 2000 The Rockefeller University Press


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