Virally delivered cytokines alter the immune response to future lung infections

James Harker, Alexander Bukreyev, Peter L. Collins, Belinda Wang, Peter J M Openshaw, John S. Tregoning

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Respiratory syncytial virus (RSV) is an important cause of infant morbidity and mortality worldwide and is increasingly recognized to have a role in the development and exacerbation of chronic lung diseases. There is no effective vaccine, and we reasoned that it might be possible to skew the immune system towards beneficial nonpathogenic responses by selectively priming protective T-cell subsets. We therefore tested recombinant RSV (rRSV) candidates expressing prototypic murine Th1 (gamma interferon [IFN-γ]) or Th2 (interleukin-4 [IL-4]) cytokines, with detailed monitoring of responses to subsequent infections with RSV or (as a control) influenza A virus. Although priming with either recombinant vector reduced viral load during RSV challenge, enhanced weight loss and enhanced pulmonary influx of RSV-specific CD8+ T cells were observed after challenge in mice primed with rRSV/IFN-γ. By contrast, rRSV/IL-4-primed mice were protected against weight loss during secondary challenge but showed airway eosinophilia. When rRSV/IL-4-primed mice were challenged with influenza virus, weight loss was attenuated but was again accompanied by marked airway eosinophilia. Thus, immunization directed toward enhancement of Th1 responses reduces viral load but is not necessarily protective against disease. Counter to expectation, Th2-biased responses were more beneficial but also influenced the pathological effects of heterologous viral challenge.

Original languageEnglish (US)
Pages (from-to)13105-13111
Number of pages7
JournalJournal of Virology
Volume81
Issue number23
DOIs
StatePublished - Dec 2007
Externally publishedYes

Fingerprint

Respiratory Syncytial Viruses
Interleukin-4
Weight Loss
cytokines
interleukin-4
lungs
immune response
Eosinophilia
Cytokines
Viral Load
Lung
viruses
eosinophilia
weight loss
mice
viral load
Infection
infection
Respiratory Syncytial Virus Infections
T-lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Harker, J., Bukreyev, A., Collins, P. L., Wang, B., Openshaw, P. J. M., & Tregoning, J. S. (2007). Virally delivered cytokines alter the immune response to future lung infections. Journal of Virology, 81(23), 13105-13111. https://doi.org/10.1128/JVI.01544-07

Virally delivered cytokines alter the immune response to future lung infections. / Harker, James; Bukreyev, Alexander; Collins, Peter L.; Wang, Belinda; Openshaw, Peter J M; Tregoning, John S.

In: Journal of Virology, Vol. 81, No. 23, 12.2007, p. 13105-13111.

Research output: Contribution to journalArticle

Harker, J, Bukreyev, A, Collins, PL, Wang, B, Openshaw, PJM & Tregoning, JS 2007, 'Virally delivered cytokines alter the immune response to future lung infections', Journal of Virology, vol. 81, no. 23, pp. 13105-13111. https://doi.org/10.1128/JVI.01544-07
Harker, James ; Bukreyev, Alexander ; Collins, Peter L. ; Wang, Belinda ; Openshaw, Peter J M ; Tregoning, John S. / Virally delivered cytokines alter the immune response to future lung infections. In: Journal of Virology. 2007 ; Vol. 81, No. 23. pp. 13105-13111.
@article{a7f50fda4a8246bab0b149e8e9b6991b,
title = "Virally delivered cytokines alter the immune response to future lung infections",
abstract = "Respiratory syncytial virus (RSV) is an important cause of infant morbidity and mortality worldwide and is increasingly recognized to have a role in the development and exacerbation of chronic lung diseases. There is no effective vaccine, and we reasoned that it might be possible to skew the immune system towards beneficial nonpathogenic responses by selectively priming protective T-cell subsets. We therefore tested recombinant RSV (rRSV) candidates expressing prototypic murine Th1 (gamma interferon [IFN-γ]) or Th2 (interleukin-4 [IL-4]) cytokines, with detailed monitoring of responses to subsequent infections with RSV or (as a control) influenza A virus. Although priming with either recombinant vector reduced viral load during RSV challenge, enhanced weight loss and enhanced pulmonary influx of RSV-specific CD8+ T cells were observed after challenge in mice primed with rRSV/IFN-γ. By contrast, rRSV/IL-4-primed mice were protected against weight loss during secondary challenge but showed airway eosinophilia. When rRSV/IL-4-primed mice were challenged with influenza virus, weight loss was attenuated but was again accompanied by marked airway eosinophilia. Thus, immunization directed toward enhancement of Th1 responses reduces viral load but is not necessarily protective against disease. Counter to expectation, Th2-biased responses were more beneficial but also influenced the pathological effects of heterologous viral challenge.",
author = "James Harker and Alexander Bukreyev and Collins, {Peter L.} and Belinda Wang and Openshaw, {Peter J M} and Tregoning, {John S.}",
year = "2007",
month = "12",
doi = "10.1128/JVI.01544-07",
language = "English (US)",
volume = "81",
pages = "13105--13111",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "23",

}

TY - JOUR

T1 - Virally delivered cytokines alter the immune response to future lung infections

AU - Harker, James

AU - Bukreyev, Alexander

AU - Collins, Peter L.

AU - Wang, Belinda

AU - Openshaw, Peter J M

AU - Tregoning, John S.

PY - 2007/12

Y1 - 2007/12

N2 - Respiratory syncytial virus (RSV) is an important cause of infant morbidity and mortality worldwide and is increasingly recognized to have a role in the development and exacerbation of chronic lung diseases. There is no effective vaccine, and we reasoned that it might be possible to skew the immune system towards beneficial nonpathogenic responses by selectively priming protective T-cell subsets. We therefore tested recombinant RSV (rRSV) candidates expressing prototypic murine Th1 (gamma interferon [IFN-γ]) or Th2 (interleukin-4 [IL-4]) cytokines, with detailed monitoring of responses to subsequent infections with RSV or (as a control) influenza A virus. Although priming with either recombinant vector reduced viral load during RSV challenge, enhanced weight loss and enhanced pulmonary influx of RSV-specific CD8+ T cells were observed after challenge in mice primed with rRSV/IFN-γ. By contrast, rRSV/IL-4-primed mice were protected against weight loss during secondary challenge but showed airway eosinophilia. When rRSV/IL-4-primed mice were challenged with influenza virus, weight loss was attenuated but was again accompanied by marked airway eosinophilia. Thus, immunization directed toward enhancement of Th1 responses reduces viral load but is not necessarily protective against disease. Counter to expectation, Th2-biased responses were more beneficial but also influenced the pathological effects of heterologous viral challenge.

AB - Respiratory syncytial virus (RSV) is an important cause of infant morbidity and mortality worldwide and is increasingly recognized to have a role in the development and exacerbation of chronic lung diseases. There is no effective vaccine, and we reasoned that it might be possible to skew the immune system towards beneficial nonpathogenic responses by selectively priming protective T-cell subsets. We therefore tested recombinant RSV (rRSV) candidates expressing prototypic murine Th1 (gamma interferon [IFN-γ]) or Th2 (interleukin-4 [IL-4]) cytokines, with detailed monitoring of responses to subsequent infections with RSV or (as a control) influenza A virus. Although priming with either recombinant vector reduced viral load during RSV challenge, enhanced weight loss and enhanced pulmonary influx of RSV-specific CD8+ T cells were observed after challenge in mice primed with rRSV/IFN-γ. By contrast, rRSV/IL-4-primed mice were protected against weight loss during secondary challenge but showed airway eosinophilia. When rRSV/IL-4-primed mice were challenged with influenza virus, weight loss was attenuated but was again accompanied by marked airway eosinophilia. Thus, immunization directed toward enhancement of Th1 responses reduces viral load but is not necessarily protective against disease. Counter to expectation, Th2-biased responses were more beneficial but also influenced the pathological effects of heterologous viral challenge.

UR - http://www.scopus.com/inward/record.url?scp=36349032361&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36349032361&partnerID=8YFLogxK

U2 - 10.1128/JVI.01544-07

DO - 10.1128/JVI.01544-07

M3 - Article

C2 - 17855518

AN - SCOPUS:36349032361

VL - 81

SP - 13105

EP - 13111

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 23

ER -