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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Viral / biosynthesis
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Cell Movement / immunology
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Complement C3 / deficiency
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Complement C3 / genetics
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Complement C3 / physiology*
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Immunoglobulin G / biosynthesis
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Interferon-gamma / biosynthesis
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Lung / immunology*
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Lung / pathology*
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Lymphocyte Activation
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Orthomyxoviridae / immunology
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Orthomyxoviridae Infections / immunology*
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Orthomyxoviridae Infections / pathology*
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Receptors, Complement 3b / deficiency
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Receptors, Complement 3b / genetics
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Receptors, Complement 3b / physiology
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Receptors, Complement 3d / deficiency
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Receptors, Complement 3d / genetics
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Receptors, Complement 3d / physiology
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T-Lymphocytes / immunology*
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T-Lymphocytes / pathology
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T-Lymphocytes / physiology*
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Helper-Inducer / immunology
Substances
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Antibodies, Viral
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Complement C3
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Immunoglobulin G
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Receptors, Complement 3b
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Receptors, Complement 3d
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Interferon-gamma