- Title
- Pulmonary eosinophils and their role in immunopathologic responses to formalin-inactivated pneumonia virus of mice
- Creator
- Percopo, Caroline M.; Qiu, Zhijun; Phipps, Simon; Foster, Paul S.; Domachowske, Joseph B.; Rosenberg, Helene F.
- Relation
- Journal of Immunology Vol. 183, Issue 1, p. 604-612
- Publisher Link
- http://dx.doi.org/10.4049/jimmunol.0802270
- Publisher
- American Association of Immunologists
- Resource Type
- journal article
- Date
- 2009
- Description
- 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-γ, IL-5, or IL-13 in bronchoalveolar lavage fluid. However, levels of both IL-4 and CCL3 (macrophage inflammatory protein-1α) in bronchoalveolar lavage fluid were markedly diminished in PVM Ag-vaccinated, PVM-infected eosinophil-deficient mice when compared with wild-type controls.
- Subject
- human respiratory syncytial virus; hRSV; pneumonia virus of mice; vaccines
- Identifier
- http://hdl.handle.net/1959.13/806973
- Identifier
- uon:7272
- Identifier
- ISSN:0022-1767
- Language
- eng
- Reviewed
- Hits: 2672
- Visitors: 3056
- Downloads: 0
| Thumbnail | File | Description | Size | Format |
|---|