Assistant Professor Wayne State Univ. Sch. of Med., Michigan, United States
Disclosure(s):
Jiahui Ding, PhD: No financial relationships to disclose
Introduction/Rationale: Air pollution during pregnancy are associated with increased risk of abnormal immune responses in offspring, including susceptibility to respiratory infections, asthma, and allergies. The developing fetal immune system is highly vulnerable to environmental exposures, yet how volatile organic compounds such as benzene affect postnatal pulmonary immunity remains unclear.
Methods: We exposed pregnant C57BL/6 mice to benzene (5 ppm, full-body inhalation, 24 h/day) from embryonic day 0.5 (E0.5) to E17.5. Offspring were analyzed at three timepoints: fetal (E17.5), postnatal day 10 (PND10), and PND35. Fetal lungs were analyzed by qPCR, western blot, Luminex, flow cytometry, bulk RNAseq, scRNAseq, and proteomics to identify persistent transcriptomic changes. PND10 pups were intraperitoneally infected with MHV68 and evaluated at PND17 for viral susceptibility using molecular, immunological, and histological assays. PND35 offspring were intranasally challenged with LPS to assess bacterial susceptibility; bronchoalveolar lavage fluid (BALF) cytokines and alveolar immune cells were analyzed by flow cytometry. Alveolar macrophages isolated at PND35 were evaluated for inflammatory responses.
Results: Prenatal benzene exposure induced sex-dimorphic reprogramming of pulmonary immunity, with alveolar macrophages and neutrophils in both females and males adopting a persistently inflammatory state. In females, this was associated with enhanced antiviral responses but increased lung inflammation and tissue damage, linked to A20 suppression. In males, pre-activated immune cells drove exaggerated inflammatory responses upon bacterial challenge.
Conclusion: These results indicate that gestational benzene exposure programs fetal lung immune cells into a dysregulated, pro-inflammatory state, contributing to long-lasting alterations in pulmonary immunity and heightened infection susceptibility in a sex-dependent manner after birth.
