Lactose in human breast milk an inducer of innate immunity with implications for a role in intestinal homeostasis

• Published in: PloS one Vol. 8; no. 1; p. e53876
• Main Authors: Cederlund, Andreas, Kai-Larsen, Ylva, Printz, Gordana, Yoshio, Hiroyuki, Alvelius, Gunvor, Lagercrantz, Hugo, Strömberg, Roger, Jörnvall, Hans, Gudmundsson, Gudmundur H, Agerberth, Birgitta
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.01.2013; Public Library of Science (PLoS)
• Subjects: Adaptive systems; Antagonists; Anti-Infective Agents - chemistry; Anti-Infective Agents - immunology; Anti-Infective Agents - isolation & purification; Antimicrobial Cationic Peptides - genetics; Antimicrobial Cationic Peptides - metabolism; Antimicrobial peptides; Baby foods; Biochemistry; Biology; Biophysics; Breast milk; Breastfeeding & lactation; Cell Line; Childrens health; Chromatography; Disease; Epithelial Cells; Esters; Gene expression; Genes; Health aspects; Health risks; Homeostasis; Homeostasis - immunology; Homeostasis - physiology; Humans; Immune system; Immunity; Immunity, Innate; Infants; Infections; Innate immunity; Intestinal Mucosa - metabolism; Intestine; Intestines - immunology; Intestines - microbiology; Kinases; Lactose; Lactose - chemistry; Lactose - immunology; Lactose - isolation & purification; Lactose intolerance; Macrophages; Mammals; Mass spectrometry; Mass spectroscopy; Medicin och hälsovetenskap; Microbiota; Milk; Milk, Human - chemistry; Milk, Human - immunology; Milk, Human - microbiology; Monocytes; Monocytes - chemistry; Monocytes - cytology; Neonates; Newborn babies; NMR; Nuclear magnetic resonance; Peptides; Phenylbutyric acid; Postpartum; Probiotics; Proteins; Synergistic effect; Sweden
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0053876

Postpartum, infants have not yet established a fully functional adaptive immune system and are at risk of acquiring infections. Hence, newborns are dependent on the innate immune system with its antimicrobial peptides (AMPs) and proteins expressed at epithelial surfaces. Several factors in breast milk are known to confer immune protection, but which the decisive factors are and through which manner they work is unknown. Here, we isolated an AMP-inducing factor from human milk and identified it by electrospray mass spectrometry and NMR to be lactose. It induces the gene (CAMP) that encodes the only human cathelicidin LL-37 in colonic epithelial cells in a dose- and time-dependent manner. The induction was suppressed by two different p38 antagonists, indicating an effect via the p38-dependent pathway. Lactose also induced CAMP in the colonic epithelial cell line T84 and in THP-1 monocytes and macrophages. It further exhibited a synergistic effect with butyrate and phenylbutyrate on CAMP induction. Together, these results suggest an additional function of lactose in innate immunity by upregulating gastrointestinal AMPs that may lead to protection of the neonatal gut against pathogens and regulation of the microbiota of the infant.