Figure 1
Development of the intestinal mucosal immune system. Before birth, Peyer’s patch anlagen develop via a crosstalk between lymphoid tissue inducer (LTi) and stroma cells within the sterile environment of the womb. The small intestinal mucosa is populated by the fetal wave of γδ T lymphocytes. At birth, the murine intestinal tissue architecture is immature and undergoes several developmental changes until reaching adult state. The neonatal mucosa is characterized by a lack of crypts and crypt-residing Paneth cells, a major source of antimicrobial substances in the adult tissue. The neonatal enterocytes, however, express cathelicidin-related antimicrobial peptide (CRAMP). Birth initiates the colonization of the intestinal mucosa and microbial density in the neonate reaches plateau levels fast. The neonatal microbiota is dominated by Lactobacilli, Streptococci, and Bifidobacteria, whereas species of the Bacteriodetes phylum become prevalent only in adults. Microbial diversity in the postnatal gut is reduced about 3-fold compared with the adult situation. Despite the presence of goblet cells, the expression of the mucins muc2, muc3, and muc5ac is reduced in the neonate resulting in a thinner mucus layer. αβ T (including thymus derived regulatory T cells (tTregs) and B lymphocytes begin to populate the intestine shortly after birth, however, they display a discrete homing pattern only to the Peyer’s patches and remain naive throughout the neonatal phase. Only after weaning, the occurrence of germinal centers and activated lymphocytes is noted in the Peyer’s patches. The maturation of M cells, which are major routes of antigen uptake in the adult, also occurs after the second week of life. The effector sites lamina propria and the intraepithelial compartment are populated by lymphocytes only after weaning. Formation of cryptopatches is noted after birth and their further maturation into isolated lymphoid follicles (ILFs) is dependent on the presence of a microbiota. During the postnatal phase, many bioactive factors are supplied by maternal breast milk including cytokines, growth factors, as well as secretory immunoglobulin A (SIgA). Endogenous SIgA is only produced by plasma cells in the adult mucosal tissue.
