The chemokine MIP1alpha/CCL3 determines pathology in primary RSV infection by regulating the balance of T cell populations in the murine lung.
BACKGROUND
CD8 T cells assist in the clearance of respiratory syncytial virus (RSV) infection from the lungs. However, disease after RSV infection is in part caused by excessive T cell activity, and a balance is therefore needed between beneficial and harmful cellular immune responses. The chemokine CCL3 (MIP1alpha) is produced following RSV infection and is broadly chemotactic for both T cells and natural killer (NK) cells. We therefore investigated its role in RSV disease.


RESULTS
CCL3 was produced biphasically, in both the early (day 1) and late (day 6-7) stages of infection. CCL3 depletion did not alter the recruitment of natural killer (NK) cells to the lungs during the early stage, but depletion did affect the later adaptive phase. While fewer T cells were recruited to the lungs of either CCL3 knockout or anti-CCL3 treated RSV infected mice, more RSV-specific pro-inflammatory T cells were recruited to the lung when CCL3 responses were impaired. This increase in RSV-specific pro-inflammatory T cells was accompanied by increased weight loss and illness after RSV infection.


CONCLUSIONS
CCL3 regulates the balance of T cell populations in the lung and can alter the outcome of RSV infection. Understanding the role of inflammatory mediators in the recruitment of pathogenic T cells to the lungs may lead to novel methods to control RSV disease.
Tregoning
John S
JS
Department of Respiratory Medicine, The Centre for Respiratory Infections Research, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Pribul
Philippa K
PK
Pennycook
Alasdair M J
AM
Hussell
Tracy
T
Wang
Belinda
B
Lukacs
Nicholas
N
Schwarze
Jurgen
J
Culley
Fiona J
FJ
Openshaw
Peter J M
PJ
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D054405:Chemokine CCL3 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000906:Antibodies; C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D014409:Tumor Necrosis Factor-alpha