title: Lactose in human breast milk an inducer of innate immunity with implications for a role in intestinal homeostasis.
abstract: 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.
authors: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors: Andreas
authors: A
authors: Cederlund
authors: Ylva
authors: Y
authors: Kai-Larsen
authors: Gordana
authors: G
authors: Printz
authors: Hiroyuki
authors: H
authors: Yoshio
authors: Gunvor
authors: G
authors: Alvelius
authors: Hugo
authors: H
authors: Lagercrantz
authors: Roger
authors: R
authors: Strömberg
authors: Hans
authors: H
authors: Jörnvall
authors: Gudmundur H
authors: GH
authors: Gudmundsson
authors: Birgitta
authors: B
authors: Agerberth
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells; D006706:Homeostasis / Q000276:immunology / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D007785:Lactose / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification; D008895:Milk, Human / Q000737:chemistry / Q000276:immunology / Q000382:microbiology; D009000:Monocytes / Q000737:chemistry / Q000166:cytology; D054804:Cathelicidins
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D007785:Lactose; D054804:Cathelicidins