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Effect of lack of Interleukin‐4, Interleukin‐12, Interleukin‐18, or the Interferon‐γ receptor on virus replication, cytokine response, and lung pathology during respiratory syncytial virus infection in mice
Author(s) -
Boelen Anita,
Kwakkel Joan,
Barends Marion,
de Rond Lia,
Dormans Jan,
Kimman Tjeerd
Publication year - 2002
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.2180
Subject(s) - bronchiolitis , immunology , cytokine , histopathology , virus , immune system , interleukin 4 , interferon , interleukin , biology , paramyxoviridae , mononegavirales , interleukin 5 , pneumovirinae , virology , medicine , viral disease , pathology
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 IFNγR −/− , 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. IFNγ‐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 IFNγ 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 IFNγ signalling leads to aggravated pulmonary pathology. This is not caused by enhanced viral load. J. Med. Virol. 66:552–560, 2002. © 2002 Wiley‐Liss, Inc.