Cutting edge: Eosinophils do not contribute to respiratory syncytial virus vaccine-enhanced disease

Elaine M Castilow; Kevin L Legge; Steven M Varga

doi:10.4049/jimmunol.181.10.6692

Back

Cutting edge: Eosinophils do not contribute to respiratory syncytial virus vaccine-enhanced disease

Journal article

Peer reviewed

Cutting edge: Eosinophils do not contribute to respiratory syncytial virus vaccine-enhanced disease

Elaine M Castilow, Kevin L Legge and Steven M Varga

The Journal of immunology (1950), Vol.181(10), pp.6692-6696

11/15/2008

DOI: 10.4049/jimmunol.181.10.6692

PMCID: PMC2596668

PMID: 18981084

View Online

Abstract

Respiratory syncytial virus (RSV) infection of BALB/c mice previously immunized with a recombinant vaccinia virus (vacv) expressing the attachment (G) protein of RSV (vacvG) results in pulmonary eosinophilia, which mimics the response of formalin-inactivated RSV-vaccinated children, as well as increased weight loss, clinical illness, and enhanced pause (Penh). We show that RSV infection of eosinophil-deficient mice previously immunized with vacvG results in the development of increased weight loss, clinical illness, and Penh similar to that in wild-type controls. These measures of RSV vaccine-enhanced disease are dependent upon STAT4. Interestingly, neither IL-12 nor IL-23, the two most common STAT4-activating cytokines, proved necessary for the development of disease. We demonstrate that IFN-gamma, which is produced following STAT4 activation, contributes to clinical illness and increased Penh, but not weight loss. Our results have important implications for future RSV vaccine design, suggesting that enhancing a Th1 response may exacerbate disease.

Respiratory Syncytial Virus Vaccines - immunology

Pulmonary Eosinophilia - virology

Respiratory Syncytial Viruses - immunology

STAT4 Transcription Factor - metabolism

Viral Proteins - immunology

Interferon-gamma - metabolism

Vaccines, Synthetic - immunology

Th1 Cells - immunology

Eosinophils - immunology

Respiratory Syncytial Virus Infections - immunology

Interleukin-23 - metabolism

Mice, Mutant Strains

Respiratory Syncytial Virus Infections - prevention & control

STAT4 Transcription Factor - immunology

Pulmonary Eosinophilia - immunology

Interleukin-12 - metabolism

STAT6 Transcription Factor - metabolism

STAT6 Transcription Factor - immunology

Interleukin-23 - immunology

Animals

Interferon-gamma - immunology

Interleukin-12 - immunology

Immunologic Memory

Mice

Mice, Inbred BALB C

Details

Title: Subtitle: Cutting edge: Eosinophils do not contribute to respiratory syncytial virus vaccine-enhanced disease
Creators: Elaine M Castilow - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA
Kevin L Legge
Steven M Varga
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.181(10), pp.6692-6696
DOI: 10.4049/jimmunol.181.10.6692
PMID: 18981084
PMCID: PMC2596668
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: R01 AI063520-02 / NIAID NIH HHS R01 AI063520 / NIAID NIH HHS AI 063520 / NIAID NIH HHS
Language: English
Date published: 11/15/2008
Academic Unit: Graduate College Admin and Gen; Microbiology and Immunology; Pathology
Record Identifier: 9984046902302771

Metrics

17 Record Views

47 Times Cited - Web of Science

See more details