title: Fetal exposure to ethanol has long-term effects on the severity of influenza virus infections.
abstract: Alcohol use by pregnant women is a significant public health issue despite well-described risks to the fetus including physical and intellectual growth retardation and malformations. Although clinical studies are limited, they suggest that in utero alcohol exposure also results in significant immune deficiencies in naive neonates. However, little is known about fetal alcohol exposure (FAE) effects on adult infections. Therefore, to determine the long-term effects of FAE on disease susceptibility and the adult immune system, we infected FAE adult mice with influenza virus. In this study, we demonstrate that mice exposed to ethanol during gestation and nursing exhibit enhanced disease severity as well as increased and sustained pulmonary viral titers following influenza virus infection. Secondary exposure to alcohol as an adult further exacerbates these effects. Moreover, we demonstrate that FAE mice have impaired adaptive immune responses, including decreased numbers of virus-specific pulmonary CD8 T cells, a decreased size and frequency of pulmonary B cell foci, and reduced production of influenza-specific Ab following influenza infection. Together, our results suggest that FAE induces significant and long-term defects in immunity and susceptibility to influenza virus infection and that FAE individuals could be at increased risk for severe and fatal respiratory infections.
authors.affiliation: Department of Pathology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Jodi
authors.initials: J
authors.lastname: McGill
authors.forename: David K
authors.initials: DK
authors.lastname: Meyerholz
authors.forename: Michelle
authors.initials: M
authors.lastname: Edsen-Moore
authors.forename: Betty
authors.initials: B
authors.lastname: Young
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Coleman
authors.forename: Annette J
authors.initials: AJ
authors.lastname: Schlueter
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Waldschmidt
authors.forename: Robert T
authors.initials: RT
authors.lastname: Cook
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Legge
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053121:Influenza A Virus, H2N2 Subtype / Q000276:immunology*; D018655:Lymphocyte Count; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D015996:Survival Rate; D013997:Time Factors
chemical_list: D000431:Ethanol