CD59a deficiency exacerbates influenza-induced lung inflammation through complement-dependent and -independent mechanisms.
Influenza-specific immune activity not only promotes virus clearance but also causes immunopathology, thereby underlining the importance of mounting a measured anti-viral immune response. Since complement bridges both the innate and adaptive immune systems and has been implicated in defence against influenza, the role of the complement regulator CD59a in modulating the response to influenza was explored. For this purpose, immune responses to influenza virus, strain E61-13-H17, in mice deficient in the complement regulator protein CD59a (Cd59a(-/-) mice) were compared to those in wild-type mice. The severity of lung inflammation was significantly enhanced in the lungs of Cd59a(-/-) mice with increased numbers of infiltrating neutrophils and CD4(+) T cells. When complement was inhibited using soluble complement receptor 1, the frequency of lung-infiltrating neutrophils in influenza-infected Cd59a(-/-) mice was much reduced whilst numbers of CD4(+) T cells remained unchanged. These results demonstrate that CD59a, previously defined as a complement regulator, modulates both the innate and adaptive immune response to influenza virus by both complement-dependent and -independent mechanisms.
Longhi
M Paula
MP
Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Cardiff, UK. mlonghi@mail.rockefeller.edu
Williams
Anwen
A
Wise
Matthew
M
Morgan
B Paul
BP
Gallimore
Awen
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018957:CD59 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D009980:Influenza A virus / Q000276:immunology; D008171:Lung Diseases / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology
D018957:CD59 Antigens; D003165:Complement System Proteins