Ingested soluble CD14 contributes to the functional pool of circulating sCD14 in mice
Copyright policy )Ingested soluble CD14 contributes to the functional pool of circulating sCD14 in mice
Soluble CD14 (sCD14) is a pattern recognition receptor and Toll-like co-receptor observed in human milk (5-26μg/mL) and other bodily fluids such as blood (3μg/mL). The most well defined role of sCD14 is to recognize lipopolysaccharide of Gram-negative bacteria and signal an immune response through Toll-like receptor 4 (TLR4). Previous research has shown ingested sCD14 to transfer from the gastrointestinal tract and into the blood stream in neonatal rats. The contribution of human milk sCD14 to circulating levels in the infant and the functionality of the protein, however, remained unknown. Using CD14(-/-) mouse pups fostered to wild type (WT) mothers expressing sCD14 in their milk, we show herein that ingestion of sCD14 resulted in blood sCD14 levels up 0.16±0.09μg/mL. This represents almost one-third (26.7%) of the circulating sCD14 observed in WT pups fostered to WT mothers (0.60±0.14μg/mL). We also demonstrate that ingested-sCD14 transferred to the blood remains functional in its ability to recognize lipopolysaccharide as demonstrated by a significant increase in immune response (IL-6 and TNF-α) in CD14(-/-) pups fostered to WT mothers in comparison to control animals (P=0.002 and P=0.007, respectively). Using human intestinal cells (Caco-2), we also observed a significant decrease in sCD14 transcytosis when TLR4 was knocked down (P<0.001), suggesting sCD14 transfer involves TLR4. The bioavailability of human milk sCD14 established in this report confirms the importance of human milk proteins for the infant and demonstrates the need to improve infant formulas which are lacking in immune proteins such as sCD14.
Lipopolysaccharides, Mice, 129 Strain, Immunology, Lipopolysaccharide Receptors, Gene Expression, Necrotizing enterocolitis, Immunology and Allergy, Animals, Humans, Lactation, TLR4, Mice, Knockout, Interleukin-6, Reverse Transcriptase Polymerase Chain Reaction, Human milk, Infant, Hematology, Feeding Behavior, sCD14, Animals, Suckling, Mice, Inbred C57BL, Protein Transport, Milk, Animals, Newborn, Microscopy, Fluorescence, RNA Interference, Caco-2 Cells, CD14, Transcytosis, HT29 Cells
Lipopolysaccharides, Mice, 129 Strain, Immunology, Lipopolysaccharide Receptors, Gene Expression, Necrotizing enterocolitis, Immunology and Allergy, Animals, Humans, Lactation, TLR4, Mice, Knockout, Interleukin-6, Reverse Transcriptase Polymerase Chain Reaction, Human milk, Infant, Hematology, Feeding Behavior, sCD14, Animals, Suckling, Mice, Inbred C57BL, Protein Transport, Milk, Animals, Newborn, Microscopy, Fluorescence, RNA Interference, Caco-2 Cells, CD14, Transcytosis, HT29 Cells
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).8 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Average
Citations provided by BIP!Popularity provided by BIP!