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Neonatal immune development

In both humans and mice, the neonatal immune system is immature and exhibits a propensity towards immune pathways associated with allergy, and an underdeveloped ability to mount immune responses against infections. Under normal circumstances the immune system matures over time and reaches a homeostasis where immune responsiveness and inflammation are in balance. However, the characteristics of this maturation process and the signals that drive it are poorly understood.

The intestinal and respiratory tracts are sterile at birth and undergo profound changes during the neonatal period when they are first exposed to environmental microbes. Although very little is currently known about the microbiota of the respiratory tract, the exact makeup of an individual’s intestinal microbiota appears to be determined by factors present during early childhood. These include the type of birth (natural versus caesarean), diet (formula versus breast-milk), early use of antibiotics and environmental conditions.

We are studying the mechanisms through which the immune system matures during the perinatal period. Focus is placed upon how environmental exposures (prenatally or postnatally) influence this developmental process, and what consequences these environments have upon susceptibility to respiratory diseases in adulthood. (Gollwitzer et al).

Neonates are predisposed to strong Th2 allergic responses in the lung, which then are reduced to "normal" adult levels due to PD-L1 induced T regulatory cells that protect against asthma. Blockade of PD-L1 with neutralising antibodies, or by infection with RSV, maintains the increased susceptibility to allergy through to adulthood.