Differential chemokine expression following respiratory virus infection reflects Th1- or Th2-biased immunopathology.
Respiratory syncytial virus (RSV) is a major viral pathogen of infants that also reinfects adults. During RSV infection, inflammatory host cell recruitment to the lung plays a central role in determining disease outcome. Chemokines mediate cell recruitment to sites of inflammation and are influenced by, and influence, the production of cytokines. We therefore compared chemokine production in a mouse model of immunopathogenic RSV infection in which either Th1 or Th2 immunopathology is induced by prior sensitization to individual RSV proteins. Chemokine expression profiles were profoundly affected by the nature of the pulmonary immunopathology: "Th2" immunopathology in BALB/c mice was associated with increased and prolonged expression of CCL2 (MCP-1), CXCL10 (IP-10), and CCL11 (eotaxin) starting within 24 h of challenge. C57BL/6 mice with "Th2" pathology (enabled by a deficiency of CD8+ cells) also showed increased CCL2 production. No differences in chemokine receptor expression were detected. Chemokine blockers may therefore be of use for children with bronchiolitis.
Culley
Fiona J
FJ
Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, St Mary's Campus, London W2 1PG, United Kingdom.
Pennycook
Alasdair M J
AM
Tregoning
John S
JS
Hussell
Tracy
T
Openshaw
Peter J M
PJ
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015967:Gene Expression Regulation, Viral; D008168:Lung / Q000378:metabolism / Q000821:virology; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*
D018925:Chemokines; D012333:RNA, Messenger; D019707:Receptors, Chemokine