Pulmonary eosinophils and their role in immunopathologic responses to formalin-inactivated pneumonia virus of mice.
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 approximately 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-gamma, IL-5, or IL-13 in bronchoalveolar lavage fluid. However, levels of both IL-4 and CCL3 (macrophage inflammatory protein-1alpha) in bronchoalveolar lavage fluid were markedly diminished in PVM Ag-vaccinated, PVM-infected eosinophil-deficient mice when compared with wild-type controls.
Percopo
Caroline M
CM
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Qiu
Zhijun
Z
Phipps
Simon
S
Foster
Paul S
PS
Domachowske
Joseph B
JB
Rosenberg
Helene F
HF
D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology; D002460:Cell Line; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D005404:Fixatives; D005557:Formaldehyde; D006967:Hypersensitivity / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D029122:Murine pneumonia virus / Q000254:growth & development / Q000276:immunology*; D018186:Pneumovirus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*
D000956:Antigens, Viral; D005404:Fixatives; D015164:Vaccines, Inactivated; D014765:Viral Vaccines; D005557:Formaldehyde