Effect of lack of Interleukin-4, Interleukin-12, Interleukin-18, or the Interferon-gamma receptor on virus replication, cytokine response, and lung pathology during respiratory syncytial virus infection in mice.
RSV is an important cause of bronchiolitis in infants. Immunopathology may play a role in RSV-induced bronchiolitis and severe RSV-induced disease has been associated with a Th2 type immune response. The aim of the study was to identify cytokine pathways that are crucial in influencing RSV-induced disease. For that purpose we inoculated IFNgammaR-/-, IL-12-/-, IL-18-/-, or IL-4-/- mice with RSV. We observed that an RSV infection resulted in a predominant Th1 cytokine response associated with slight bronchiolitis and alveolitis. Pulmonary histopathology was only aggravated in IFN R-/- mice, characterised by eosinophilic influx around the bronchioles. Despite subtle changes in cytokine expression, no differences in histopathology were observed in IL-12-/- and IL-18-/- mice. Deficiency of IL-4 has no effect on RSV-induced Th1 cytokines and pulmonary histopathology. IFNgamma-receptor deficiency during primary RSV infection resulted in a disturbed Th1 response based on increased IL-4, IL-5, and IL-13 expression and the presence of eosinophils in the lungs. It is concluded that IFNgamma signalling is required for a pronounced Th1 response to RSV while IL-12 and IL-18 are not. A shift in the balance between Th1 and Th2 towards a Th2 response induced by missing IFNgamma signalling leads to aggravated pulmonary pathology. This is not caused by enhanced viral load.
Boelen
Anita
A
Research Laboratory for Infectious Diseases, National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
Kwakkel
Joan
J
Barends
Marion
M
de Rond
Lia
L
Dormans
Jan
J
Kimman
Tjeerd
T
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics; D020382:Interleukin-18 / Q000172:deficiency / Q000235:genetics; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics; D008168:Lung / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D018357:Respiratory Syncytial Virus Infections / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity* / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication; D000096743:Interferon gamma Receptor
D016207:Cytokines; D018664:Interleukin-12; D020382:Interleukin-18; D015847:Interleukin-4; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor