Immune Cell–Mediated Protection of the Mammary Gland and the Infant during Breastfeeding

Abstract

Breastfeeding has been regarded first and foremost as a means of nutrition for infants, providing essential components for their unique growth and developmental requirements. However, breast milk is also rich in immunologic factors, highlighting its importance as a mediator of protection. In accordance with its evolutionary origin, the mammary gland offers via the breastfeeding route continuation of the maternal to infant immunologic support established in utero. At birth, the infant's immune system is immature, and although it was exposed to the maternal microbial flora during pregnancy, it experiences an abrupt change in its microbial environment during and after birth, which is challenging and renders the infant highly susceptible to infection. Active and passive immunity protects the infant via breast milk, which is rich in immunoglobulins, lactoferrin, lysozyme, cytokines, and numerous other immunologic factors, including maternal leukocytes. Breast milk leukocytes provide active immunity and promote development of immunocompetence in the infant. Additionally, it has been speculated that they play a role in the protection of the mammary gland from infection. Leukocytes are thought to exert these functions via phagocytosis, secretion of antimicrobial factors and/or antigen presentation in both the mammary gland and the gastrointestinal tract of the infant, and also in other infant tissues, where they are transported via the systemic circulation. Recently, it has been demonstrated that breast milk leukocytes respond dynamically to maternal as well as infant infections, and are fewer in nonexclusively compared with exclusively breastfeeding dyads, further emphasizing their importance for both the mother and infant. This review summarizes the current knowledge of human milk leukocytes and factors influencing them, and presents recent novel findings supporting their potential as a diagnostic marker for infections of the lactating breast and of the breastfed infant.

Phagocytosis of a Model Human Immunodeficiency Virus Target by Human Breast Milk Leukocytes Is Predominantly Granulocyte-Driven When Elicited by Specific Antibody

“…Past the colostral stage, human BM contains *10 3 -10 4 leukocytes per milliliter, [21][22][23][24][25] and it has been shown recently that as BM matures over the first month, the neutrophil concentration increases. 26 Importantly, various animal studies have demonstrated that maternal leukocytes in BM are FIG.…”

“…[21][22][23][24] Given that BM contains *10 2 -10 5 leukocytes per milliliter, it can be estimated that breastfed infants ingest *10 5 -10 8 maternal leukocytes daily. 25 Varied cell classification methods have found macrophages and neutrophils to dominate in colostrum (40-50% of total leukocytes, respectively), followed by lymphocytes (5-10%), although very few studies of BM composition beyond early lactation exist. 21 Colostrum exhibits a significantly higher cell count than mature milk.…”

“…26 Various in vivo studies have demonstrated that maternal leukocytes provide critical immunity to the infant and are functional well beyond these sites of initial ingestion. 25,[27][28][29][30][31][32] All maternally derived cells ingested by the infant have the potential to perform immune functions alongside or to compensate for the infant's own leukocytes. 33 This is likely in conjunction with other BM components, such as maternal Abs.…”

Leptin Levels Are Higher in Whole Compared to Skim Human Milk, Supporting a Cellular Contribution

“…Additionally, flow cytometric analysis of HM cells has revealed that the majority of lactocytes and stem cells contain the leptin protein [22]. Given that lactocytes are the dominant cell type in mature whole HM when both the mother and infant are healthy [1,48,49,53,54], it is likely that lactocytes contribute significantly to HM leptin levels. Indeed, the cellular fraction of HM can constitute a significant portion of milk, comparable to its skim and fat fractions [1,31].…”

Beneficios inmunológicos de la leche humana para la madre y el niño. Revisión sistemática

“…La leche materna protege de forma activa y pasiva al lactante, gracias a su riqueza en inmunoglobulinas, lactoferrina, lisozima, citoquinas y otros numerosos factores inmunológicos, como leucocitos maternos, que proporcionan inmunidad activa y promueven el desarrollo de la inmunocompetencia del bebé (68). En este sentido, se han descrito importantes hallazgos a través de diversos estudios, al mostrar el papel protector que ejerce la LM ante diversas enfermedades.…”