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Fetal Exposure to Ethanol Has Long-Term Effects on the Severity of Influenza Virus Infections¹

Jodi McGill^*,, David K. Meyerholz^*, Michelle Edsen-Moore^*, Betty Young^*, Ruth A. Coleman^*, Annette J. Schlueter^*,, Thomas J. Waldschmidt^*,, Robert T. Cook^* and Kevin L. Legge^2,*,

^* Department of Pathology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant AA-014405 (to R.T.C.) and Department of Pathology Start-Up Funds (to K.L.L.).

² Address correspondence and reprint requests to Dr. Kevin L. Legge, Department of Pathology, 1036 Medical Laboratories, 200 Hawkins Drive, Iowa City, IA 52242. E-mail address: kevin-legge{at}uiowa.edu

³ Abbreviations used in this paper: EtOH, ethanol; aM, alveolar macrophage; DC, dendritic cell; FAE, fetal alcohol exposure; MDCK, Madin-Darby canine kidney; NP, influenza nucleocapsid protein; p.i., postinfection.

⁴ The online version of this article contains supplemental material.