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* Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
Priority Research Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and the Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia; and
Department of Pediatrics, Upstate Medical University, Syracuse, NY 13210
Enhanced disease is the term used to describe the aberrant Th2-skewed responses to naturally acquired human respiratory syncytial virus (hRSV) infection observed in individuals vaccinated with formalin-inactivated viral Ags. Here we explore this paradigm with pneumonia virus of mice (PVM), a pathogen that faithfully reproduces features of severe hRSV infection in a rodent host. We demonstrate that PVM infection in mice vaccinated with formalin-inactivated Ags from PVM-infected cells (PVM Ags) yields Th2-skewed hypersensitivity, analogous to that observed in response to hRSV. Specifically, we detect elevated levels of IL-4, IL-5, IL-13, and eosinophils in bronchoalveolar lavage fluid of PVM-infected mice that were vaccinated with PVM Ags, but not among mice vaccinated with formalin-inactivated Ags from uninfected cells (control Ags). Interestingly, infection in PVM Ag-vaccinated mice was associated with a 
10-fold reduction in lung virus titer and protection against weight loss when compared with infected mice vaccinated with control Ags, despite the absence of serum-neutralizing Abs. Given recent findings documenting a role for eosinophils in promoting clearance of hRSV in vivo, we explored the role of eosinophils in altering the pathogenesis of disease with eosinophil-deficient mice. We found that eosinophil deficiency had no impact on virus titer in PVM Ag-vaccinated mice, nor on weight loss or levels of CCL11 (eotaxin-1), IFN-
, IL-5, or IL-13 in bronchoalveolar lavage fluid. However, levels of both IL-4 and CCL3 (macrophage inflammatory protein-1
) in bronchoalveolar lavage fluid were markedly diminished in PVM Ag-vaccinated, PVM-infected eosinophil-deficient mice when compared with wild-type controls.
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 Institute of Allergy and Infectious Diseases Division of Intramural Research funding to H.F.R.
2 Address correspondence and reprint requests to Dr. Helene F. Rosenberg, Laboratory of Allergic Diseases, Building 10, Room 11C215, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892. E-mail address: hrosenberg{at}niaid.nih.gov
3 Abbreviations used in this paper: hRSV, human respiratory syncytial virus; bRSV, bovine respiratory syncytial virus; PVM, pneumonia virus of mice.
4 The online version of this article contains supplemental material.
This article has been cited by other articles:
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  K. D. Dyer, C. M. Percopo, E. R. Fischer, S. J. Gabryszewski, and H. F. Rosenberg Pneumoviruses infect eosinophils and elicit MyD88-dependent release of chemoattractant cytokines and interleukin-6 Blood, September 24, 2009; 114(13): 2649 - 2656. [Abstract] [Full Text] [PDF]
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