Developmental Impact of Maternal Immune Activation on the Fetal Immune System and Lung

Maternal immune activation (MIA) refers to an immune response triggered in a pregnant mother by infections, inflammation, or other immune challenges that can impact offspring health. We propose aligning MIA within the framework of the developmental origins of health and disease (DOHaD) theory because it has the potential to provide mechanistic evidence for long-term outcomes of fetomaternal crosstalk disruptions. MIA models are created by exposing pregnant animals to immune-activating agents such as inosinic-polycytidylic acid (poly I:C) or lipopolysaccharide (LPS), which mimic viral or bacterial infections, respectively. Next to these acute MIA models, chronic helminth infections during pregnancy have been employed as an additional, more physiological model of infection. MIA models have helped researchers explore how maternal infections during pregnancy may impact the offspring's risk of neurodevelopmental disorders. Emerging evidence suggests that these models have a broader impact on organ development, the immune system, and, consequently, immune-related disorders such as allergies. Our review focuses on evidence derived mainly from mouse models of MIA that have investigated maternal signals, such as cytokines and microbiota, on fetal hematopoiesis, adults' immune cell compartments, including the bone marrow, and their relation to the development of offspring allergies. Where applicable, studies from other species are indicated.