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Complement component C3 promotes T-cell priming and lung migration to control acute influenza virus infection

Nature Medicine volume 8, pages 373–378 (2002)Cite this article

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-γ 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.

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Figure 1: Reduced clearance of influenza virus in C3−/− mice.
Figure 2: C3, but not CR1/CR2, is required for optimal Th cell–dependent IgG responses to influenza virus.
Figure 3: Pulmonary T-cell recruitment and effector function is controlled by C3.
Figure 4: Impaired priming of virus specific CD4+ T cells and CTLs in the absence of C3.
Figure 5: Adoptive transfer of wild-type T cells to C3−/− mice.

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Acknowledgements

We thank B. Ecabert and K. Lefrang for technical assistance, and G. Köhler for histology. A. Gallimore was supported by The Wellcome Trust (GR056527MA). The Basel Institute for Immunology was founded and supported by F. Hoffmann LaRoche.

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Authors and Affiliations

  1. Department of Environmental Sciences, Molecular Biomedicine, Swiss Federal Institute of Technology, Zurich, Switzerland

    Manfred Kopf & Brian Abel

  2. Basel Institute for Immunology, Basel, Switzerland

    Manfred Kopf & Brian Abel

  3. Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK

    Awen Gallimore

  4. The Center for Blood Research, Harvard Medical School, Boston, Massachusetts, USA

    Michael Carroll

  5. Cytos Biotechnology AG, Schlieren-Zurich, Switzerland

    Martin F. Bachmann

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Correspondence to Manfred Kopf or Martin F. Bachmann.

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Kopf, M., Abel, B., Gallimore, A. et al. Complement component C3 promotes T-cell priming and lung migration to control acute influenza virus infection. Nat Med 8, 373–378 (2002). https://doi.org/10.1038/nm0402-373

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