NLRP3 and CCR1 drive offspring asthma susceptibility following maternal RSV infection.

Abstract

Maternal infection with respiratory syncytial virus (RSV) during pregnancy has been implicated in shaping offspring respiratory outcomes, but the underlying mechanisms remain undefined. Using a murine model, we investigated how maternal RSV infection affects fetal immune programming, postnatal airway remodeling, and susceptibility to allergen-induced inflammation. Offspring of RSV-infected dams developed heightened airway inflammation and goblet cell hyperplasia following allergen challenge, accompanied by increased immune cell infiltration and airway remodeling. These effects were associated with activation of the NLRP3 inflammasome in maternal lung and altered CCR1-associated inflammatory responses in offspring lungs. Transcriptomic profiling of offspring lungs revealed enrichment of pathways related to leukocyte-mediated immunity and cytokine signaling. Pharmacologic inhibition of NLRP3 during maternal infection reduced postnatal airway inflammation and tissue remodeling in offspring. Similarly, blockade of CCR1 attenuated eosinophilic infiltration and mucus hypersecretion. These findings support a model in which maternal RSV-induced inflammasome activation is associated with NLRP3-linked immune programming and CCR1-dependent inflammatory responses in offspring.