Complement component C3 promotes T-cell priming and lung migration to control acute influenza virus infection.
The complement cascade defines an important link between the innate and the specific immune system. Here we show that mice deficient for the third component of complement (C3-/- mice) are highly susceptible to primary infection with influenza virus. C3-/- mice showed delayed viral clearance and increased viral titers in lung, whereas mice deficient for complement receptors CR1 and CR2 (Cr2-/- mice) cleared the infection normally. Priming of T-helper cells and cytotoxic T cells (CTLs) in lung-draining lymph nodes was reduced, and the recruitment into the lung of virus-specific CD4+ and CD8+ effector T cells producing interferon-gamma was severely impaired in C3-/- but not in Cr2-/- mice. Consequently, T-helper cell-dependent IgG responses were reduced in C3-/- mice but remained intact in Cr2-/- mice. These results demonstrate that complement induces specific immunity by promoting T-cell responses.
Kopf
Manfred
M
Molecular Biomedicine, Department of Environmental Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland. manfred.kopf@biomed.umnw.ethz.ch
Abel
Brian
B
Gallimore
Awen
A
Carroll
Michael
M
Bachmann
Martin F
MF
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002465:Cell Movement / Q000276:immunology; D003176:Complement C3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology*; D017463:Receptors, Complement 3b / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D017464:Receptors, Complement 3d / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000914:Antibodies, Viral; D003176:Complement C3; D007074:Immunoglobulin G; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D007371:Interferon-gamma