Mammary Immunology And Protection Of The Neonate

Colostrum and milk, secretions of mammary gland (MG) are the two components of the post-natal delivery of maternal immunity to the neonate mammals. In monogastric animals, sIgA is the predominant colostrum or milk Ig depending upon to the degree of prenatal Ig transfer, whereas in ruminant IgG1 predominate. In human/mouse high Ig transfert occurs before birth so that sIgA is the chiefest. In contrast, in ungulate as swine and ruminant absence of prenatal Ig transfert is compensated for by a IgG enriched colostrum.  These immunoglobulins by entering in the neonate blood provide the newborn with the maternal serum antibodies that arose from antigenic stimulation of the mother's systemic immune system and sustain the systemic protection of the neonate against invasive pathogens. In contrast, the passive mucosal protection of neonate mammals is dependent on the continuous supply until weaning of maternally dimeric IgA (Monogastric) and IgG1 (Ruminants), the so-called lactogenic immunity.

The Ag specificity of milk IgA similar to that of gut led to the concept of entero-mammary link which was demonstrated by migration of gut-derived IgA plasma cells in MG rather than by translocation of blood sIgA through the MG. Similarly, by analogy, a possible cellular nasal-mammary link in mammals may exist in species where a mucosal IgA response is elicited by pharyngeal tonsils of Waldeyer’s ring. Based onto the multisteps model of lymphocyte migration and of compartments we analyzed the spatio-temporal relationships between adhesion molecules, chemokines and their receptors between the gut/nasal mucosae and MG, comparatively in mouse and swine, which differ by the nasal inductor sites.

In mouse, localization of a4b7 T-cells follows MadCAM-1 development onto blood capillaries. In contrast, b7/c-IgA B plasmablasts increased in mid- and late lactation when MAdCAM-1 density plateaued; this result suggested the implication of chemoattractant factors specific of B-cell and releasing in lactation; one of these factors has now been identified as chemokine CCL28 (MEC) interacting with CCR10. VCAM-1 is present only onto large blood vessels.

In sow MG the kinetics of T and cIgA cells is similar to that in mouse and the accumulation of T cells paralleled that of TECK, whilst a4b1/a4b7/cIgA cells followed the development of MadCAM-1/VCAM-1 in lactation: furthermore, these cells share the same pattern of adhesion molecules and chemokines as those in small gut and upper respiratory tract (URT) mucosae. These data indicate the existence of a cellular URT-mammary link in addition to the entero-mammary link. Thus protection of neonate piglets may participate of both nasal-bronchial and gut mucosal protection of their nursing mother.

By comparison, absence of MadCAM-1 in ruminant MG sustain the view of the absence of link with the intestinal immune system, explaining the low levels of IgA in bovine mammary secretions.

In conclusion, knowledge of these humoral (including mammary B cell chemoattractant factor such as a recent identified peptide derived from serum amyloid A protein) and cellular factors of mucosal mammary links may pave the way of optimal route of vaccination to protect the mammary gland itself and to protect the neonate via its secretion.