title: Complement component C3 promotes T-cell priming and lung migration to control acute influenza virus infection.
abstract: 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.
authors.affiliation: Molecular Biomedicine, Department of Environmental Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland. manfred.kopf@biomed.umnw.ethz.ch
authors.forename: Manfred
authors.initials: M
authors.lastname: Kopf
authors.forename: Brian
authors.initials: B
authors.lastname: Abel
authors.forename: Awen
authors.initials: A
authors.lastname: Gallimore
authors.forename: Michael
authors.initials: M
authors.lastname: Carroll
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
mesh_terms: 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
chemical_list: D000914:Antibodies, Viral; D003176:Complement C3; D007074:Immunoglobulin G; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D007371:Interferon-gamma