Innate recognition of bacteria in human milk is mediated by a milk-derived highly expressed pattern recognition receptor, soluble CD14.
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.
Labéta
M O
MO
Department of Medicine, University of Wales, College of Medicine, Heath Park, Cardiff CF4 4XX, United Kingdom.
Vidal
K
K
Nores
J E
JE
Arias
M
M
Vita
N
N
Morgan
B P
BP
Guillemot
J C
JC
Loyaux
D
D
Ferrara
P
P
Schmid
D
D
Affolter
M
M
Borysiewicz
L K
LK
Donnet-Hughes
A
A
Schiffrin
E J
EJ
D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000276:immunology*; D002417:Cattle; D003126:Colostrum / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007225:Infant Food / Q000032:analysis; D007231:Infant, Newborn; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008895:Milk, Human / Q000276:immunology* / Q000382:microbiology*; D008969:Molecular Sequence Data; D011247:Pregnancy; D012995:Solubility
D018950:Lipopolysaccharide Receptors