Enhanced antiviral antibody secretion and attenuated immunopathology during influenza virus infection in nitric oxide synthase-2-deficient mice.
NOS2 gene-deficient (NOS2(-/-)) mice are less susceptible than wild-type (NOS2(+/+)) mice to infection with Influenza A virus. Virus titres in the lungs of influenza-infected NOS2(-/-) mice are significantly lower than those in NOS2(+/+) mice, with enhanced viral clearance in NOS2(-/-) mice dependent on gamma interferon (IFN-gamma). The current study was undertaken to ascertain the role of specific components of the immune response in promoting virus clearance in influenza-infected NOS2(-/-) mice. Levels of T cell- and natural killer cell-mediated cytotoxicity in the lungs of virus-infected mice were not significantly different between NOS2(+/+) and NOS2(-/-) mice. However, virus-infected NOS2(-/-) mice produced higher levels of virus-specific IgG2a antibody. Furthermore, more viable B cells and plasmablasts, along with greater levels of IFN-gamma, were found in NOS2(-/-) splenocyte cultures stimulated with B-cell mitogens. In addition to the early reduction in virus titres, clinical symptoms and proinflammatory cytokine production were attenuated in NOS2(-/-) mice. Thus, NOS2(-/-) B cells are capable of responding rapidly to influenza virus infection by proliferating and preferentially producing antibody of the IgG2a subtype. The relationship between viral load and the development of immunopathology is discussed.
Jayasekera
Jerome P
JP
Department of Pathology, Bosch Institute, School of Biomedical Sciences, Blackburn Building D06, University of Sydney, NSW 2006, Australia.
Vinuesa
Carola G
CG
Division of Immunology and Genetics, John Curtin School of Medical Research (JCSMR), Australian National University, Canberra, ACT 2601, Australia.
Karupiah
Gunasegaran
G
Division of Immunology and Genetics, John Curtin School of Medical Research (JCSMR), Australian National University, Canberra, ACT 2601, Australia.
King
Nicholas J C
NJC
Department of Pathology, Bosch Institute, School of Biomedical Sciences, Blackburn Building D06, University of Sydney, NSW 2006, Australia.
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D007074:Immunoglobulin G / Q000097:blood; D009980:Influenza A virus / Q000276:immunology / Q000302:isolation & purification; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D010950:Plasma Cells / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load
D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse