Maternal-neonatal model of immune protection to type 2 pulmonary inflammation

Abstract

Abstract Asthma tends to “run in families” is a concept supported by several research studies of asthma genetics, but this only explains a relatively small fraction of asthma inheritance. We are now standing this paradigm on its head by asking the opposite question: Can asthma protection be passed on from one generation to the next? Epidemiological and experimental studies have determined that the early postnatal period offers a critical window for the establishment of lung protection. Maternal milk represents a potentially important transgenerational mechanism by which offspring may acquire early-life immunity from their mothers. To study this transfer of protection we have developed a new preclinical animal model of maternal transference of immune protection. In this model, maternal exposure to endotoxin postpartum resulted in infant protection from allergic inflammation to the common indoor allergen house dust mite and to a clinical strain of Respiratory Syncytial Virus (RSV). The overall downregulation of type 2 immune responses to an allergen and a virus indicated that the mechanism of protection was common for different antigens. Metabololipidomics analysis of maternal milk from endotoxin-exposed mothers revealed elevated levels of select specialized pro-resolving mediators (SPMs) from essential fatty acids. Young animals from endotoxin-exposed mothers had overall lower allergic immune responses, which was related to altered pulmonary dendritic cell (DC) subsets. Importantly, these protective effects of asthmatic inflammation reduction were also recapitulated with the direct administration of SPMs. This study provides a novel transgenerational immunological conduit of protection in a heretofore-unexamined process