CD14: a soluble pattern recognition receptor in milk

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.