Breast milk also contains substantial amounts of intracellular adhesion molecule 1 and vascular adhesion molecule 1; low quantities of soluble S-selectin, l-selectin and CD14, which may mediate differentiation and growth of B cells [46]. Natural autoantibodies, thought to be important in the selection of the pre-immune B cell repertoire and in the development of immune tolerance,
are also detected in colostrum and in breast milk [48]. Recently, the beneficial effects of human oligosaccharides in prevention of neonatal diarrhoeal and respiratory tract infections have been highlighted [49] and [50]. Human breast milk is known to contain factors that can modulate toll-like receptor (TLR) Selleckchem PARP inhibitor signaling, including soluble TLR2, which can competitively inhibit signaling through membrane TLR2 [51], as well as a protein that inhibits TLR2-mediated and activates TLR4-mediated transcriptional responses
in human intestinal epithelial and mononuclear cells by an as-yet-unknown mechanism [52]. It has been speculated that reduced TLR2 responsiveness at birth may facilitate the normal establishment of beneficial Gram-positive bifidobacteria intestinal flora. Lipids present in human milk have been shown to inactivate GBS in vitro, providing additional benefit to protect from invasive infection at the mucosal surfaces [53]. Neonates have Rapamycin research buy low levels of SIgA and SIgM [54] thus protection from invasive pathogens enough at the mucosal surface relies on antibodies in breast milk. As antibody in breast milk is produced following antigenic stimulation of the maternal MALT and bronchial tree (bronchomammary pathway) [55], these antibodies are targeted to many infectious agents encountered by the mother both prior to birth and during the breastfeeding
period. It is currently hypothesized that SIgA represents the crucial primary protective component of breast milk [56] and [57]. SIgA protects against mucosal pathogens by immobilizing these, preventing their adherence to epithelial surfaces, or by neutralizing toxins or virulence factors. SIgA concentration is far higher in colostrum (12 mg/ml) than in that found in mature milk (1 mg/ml). A breastfed infant may ingest around 0.5–1.0 g of SIgA per day [40]. SIgA production is enhanced by Interleukin-6 (IL-6) whilst the production of secretory components is enhanced by TNF-α and TGF-β causes class switching towards B cells producing IgA [47], all of which are present in breast milk. SIgA antibodies present in breast milk are specific for numerous enteric and respiratory pathogens.