Innate Recognition of Bacteria in Human Milk Is Mediated by a Milk-derived Highly Expressed Pattern Recognition Receptor, Soluble CD14

doi:10.1084/jem.191.10.1807

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. Labéta^a, Karine Vidal^c, Julia E. Rey Nores^a, Mauricio Arias^a, Natalio Vita^d, B. Paul Morgan^b, Jean Claude Guillemot^d, Denis Loyaux^d, Pascual Ferrara^d, Daniel Schmid^c, Michael Affolter^c, Leszek K. Borysiewicz^a, Anne Donnet-Hughes^c, and Eduardo J. Schiffrin^c
^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

Correspondence to: Eduardo J. Schiffrin, Nestlé Research Center, Vers-Chez-Les-Blanc, CH 1000 Lausanne 26, Switzerland. Tel:41-21-785-8671 Fax:41-21-785-8925 E-mail:eduardo.schiffrin{at}rdls.nestle.com.

Little is known about innate immunity to bacteria after birthin the hitherto sterile fetal intestine. Breast-feeding haslong been associated with a lower incidence of gastrointestinalinfections and inflammatory and allergic diseases. We foundin human breast milk a 48-kD polypeptide, which we confirmedby mass spectrometry and sequencing to be a soluble form ofthe bacterial pattern recognition receptor CD14 (sCD14). MilksCD14 (m-sCD14) concentrations were up to 20-fold higher thanserum sCD14 from nonpregnant, pregnant, or lactating women.In contrast, lipopolysaccharide (LPS)-binding protein was atvery low levels. Mammary epithelial cells produced 48-kD sCD14.m-sCD14 mediated activation by LPS and whole bacteria of CD14negative cells, including intestinal epithelial cells, resultingin release of innate immune response molecules. m-sCD14 wasundetectable in the infant formulas and commercial (cows') milktested, although it was present in bovine colostrum. These findingsindicate a sentinel role for sCD14 in human milk during bacterialcolonization of the gut, and suggest that m-sCD14 may be involvedin modulating local innate and adaptive immune responses, thuscontrolling homeostasis in the neonatal intestine.

Key Words: innate immunity, neonatal immunity, mucosal immunity, intestinalimmune response, breast-feeding

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