The hygiene hypothesis revisited: role of materno-fetal interactions.

For 20 years, the hygiene hypothesis has dominated attempts to explain the increasing prevalence of allergic disease. A causal link between maternal innate immune response during pregnancy and disease protection in the offspring was recently demonstrated. Central to this was a systemically diffused signal that downregulated Toll-like receptor expression in placental tissues. Herein we develop the hypothesis that maternal systemic regulatory mechanisms operational during pregnancy could impact allergic disease risk of the offspring, depending on the type of inflammatory response from which they originate. Classic microbial-derived, mild, subacute inflammation provides a protective signal, whereas allergic inflammation provides a negative one. Mild, subacute inflammation of pregnant women leads to systemically diffused signals manifest in the gestation-associated tissues and by the fetus and newborn as a dampened inflammatory response. The converse is true if the mother has allergic inflammation during pregnancy. In both cases, these impact on development of the airways and of balanced immune function at birth and in early postnatal life. Thus, we seem to be at the dawn of a new incarnation of the hygiene hypothesis in which the pregnant woman's inflammatory response is crucial to determining the child's likelihood of developing allergic disease.