Prenatal smoke exposure exacerbates lung inflammatory response by modulating neutrophil infiltration to the lungs after RSV infection

Abstract

Exposure to second hand tobacco smoke (SHS) is associated with an increased frequency and severity of viral respiratory tract infections. The mechanisms of recurrence and susceptibility to viral pathogens after passive smoke exposure are multifactorial and include alteration of the structural and immunologic host defenses. Maternal smoking during pregnancy is associated with a number of adverse health effects in infants, including higher susceptibility to respiratory syncytial virus (RSV) infection and associated bronchiolitis. Given the extensive impact on human health, further studies are needed that identify the mechanisms responsible for the increased severity of respiratory viral infections in individuals exposed to cigarette smoke. In this work, we used a well-established mouse model of in-utero smoke exposure. Offspring (5-day old) were infected intranasally with RSV and sacrificed at different times post infection. Sample analysis indicated that in-utero SHS exposure led to increased lung inflammation and higher viral lung titers, as shown by lung histopathology and plaque assay, respectively. In further understanding the mechanism of inflammation, cytokine profile revealed a significant increase in CXCL1 (KC), a potent neutrophil chemoattractant. Thus, we investigated the infiltration of neutrophils in lungs of SHS and air-exposed mice. FACS analysis revealed not only that RSV-infected neonates exposed to in-utero SHS had a significant increase in neutrophil influx into airways compared to air-exposed mice, but also that their neutrophils were more activated and expressed higher levels of CXCR2. In conclusion, our results help elucidate the mechanisms underlying harmful effect of smoking during pregnancy.