CD14: A Soluble Pattern Recognition Receptor in Milk

Abstract

An innate immune system capable of distinguishing among self, non-self, and danger is a prerequisite for health. Upon antigenic challenge, pattern recognition receptors (PRRs), such as the Toll-like receptor (TLR) family of proteins, enable this system to recognize and interact with a number of microbial components and endogenous host proteins. In the healthy host, such interactions culminate in tolerance to self-antigen, dietary antigen, and commensal microorganisms but in protection against pathogenic attack. This duality implies tightly regulated control mechanisms that are not expected of the inexperienced neonatal immune system. Indeed, the increased susceptibility of newborn infants to infection and to certain allergens suggests that the capacity to handle certain antigenic challenges is not inherent. The observation that breast-fed infants experience a lower incidence of infections, inflammation, and allergies than formula-fed infants suggests that exogenous factors in milk may play a regulatory role. There is increasing evidence to suggest that upon exposure to antigen, breast milk educates the neonatal immune system in the decision-making processes underlying the immune response to microbes. Breast milk contains a multitude of factors such as immunoglobulins, glycoproteins, glycolipids, and antimicrobial peptides that, qualitatively or quantitatively, may modulate how neonatal cells perceive and respond to microbial components. The specific role of several of these factors is highlighted in other chapters in this book. However, an emerging concept is that breast milk influences the neonatal immune system's perception of "danger." Here we discuss how CD14, a soluble PRR in milk, may contribute to this education.

Complete genome sequence of the probiotic lactic acid bacteriumLactobacillus acidophilusNCFM

“…Other teichoic acid associated ORFs include a tandem set of teichoic acid biosynthesis and transport proteins (La524 and La525), another predicted biosynthetic protein (La519), two more polysaccharide transporters specific to Oantigen and teichoic acid (La1614 and La1917), along with a cell wall teichoic acid glycosylation protein (La621) ( Table 9, which is published as supporting information on the PNAS web site). An exaggerated inflammatory response from intestinal epithelial cells to Gram-negative bacteria can be tempered by teichoic acids from lactobacilli (42), suggesting an intimate involvement of teichoic acids and the immune system. The uncharacterized low GC regions and the EPS cluster are centered on two divergently oriented transposases (La1722, La1721, and La1720).…”

Ehrlichia chaffeensis TRP32 Interacts with Host Cell Targets That Influence Intracellular Survival

“…CD14 is a glycosylphosphatidylinositol-anchored protein preferentially expressed on the surfaces of monocytes/macrophages and was the first pattern recognition receptor (PRR) in the innate immune system to be described (37). It acts as a coreceptor (along with Toll-like receptor TLR4 and MD-2) for the binding of bacterial lipopolysaccharide (LPS) in the presence of lipopolysaccharide-binding protein (LBP) and other pathogen-associated molecular patterns (PAMPs) to activate several downstream signaling pathways (1).…”

Alpha-Lactalbumin in Human Milk Alters the Proteolytic Degradation of Soluble CD14 by Forming a Complex

“…Paradoxically, both sCD14 and Gram-negative bacteria are found in human milk (7,26) and yet do not seem to trigger inflammation in the GI tract of breast-fed infants or in the mammary gland of the lactating mother. This suggests that the normal physiological response of sCD14 may be altered in these compartments.…”

“…It has been demonstrated that breast-fed newborns experience a lower incidence of gastrointestinal (GI) infections including inflammatory, respiratory, and allergic disease in comparison with formula-fed infants (3)(4)(5)(6). Protection by milk has been attributed to maternal immunocompetent cells, immunoglobulins, immune reactive peptides, anti-infectious oligosaccharides, growth factors, lactoferrin, and complement components (7).…”

“…Soluble CD14 (sCD14) binds to whole bacteria and bacterial cell wall components and mediates bacterial-induced proinflammatory cytokine production from cells that typically do not express membrane-bound CD14 (11). The biology of CD14 in the breast, in milk, and in the gut is emerging (7). The average concentration of sCD14 in human milk is 25-50 g/mL, and consumption of ϳ1 liter of milk per day by breast feeding infants suggests the GI tract is exposed to milligram quantities of this potent immunostimulatory protein.…”