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Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches

  • Conference paper
Immune Responses to Biosurfaces

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 865))

Abstract

The complement system is a network of interacting fluid-phase and cell surface-associated molecules that trigger, amplify, and regulate immune and inflammatory signaling pathways. Dysregulation of this finely balanced network can destabilize host-microbe homeostasis and cause inflammatory tissue damage. Evidence from clinical and animal model-based studies suggests that complement is implicated in the pathogenesis of periodontitis, a polymicrobial community-induced chronic inflammatory disease that destroys the tooth-supporting tissues. This review discusses molecular mechanisms of complement involvement in the dysbiotic transformation of the periodontal microbiome and the resulting destructive inflammation, culminating in loss of periodontal bone support. These mechanistic studies have additionally identified potential therapeutic targets. In this regard, interventional studies in preclinical models have provided proof-of-concept for using complement inhibitors for the treatment of human periodontitis.

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Acknowledgments

The authors are supported by grants from the U.S. National Institutes of Health: DE015254, DE017138, DE021685, and DE024716 (G.H.); AI003040, AI068730, EY020633, and GM097747 (J.D.L.) and from the European Community’s Seventh Framework Programme under grant agreement number 602699 (DIREKT) (J.D.L.).

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Authors and Affiliations

  1. Department of Microbiology, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    George Hajishengallis, Tomoki Maekawa & Toshiharu Abe

  2. Department of Restorative and Preventive Sciences, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Evlambia Hajishengallis

  3. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    John D. Lambris

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  1. George Hajishengallis
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  2. Tomoki Maekawa
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  3. Toshiharu Abe
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  4. Evlambia Hajishengallis
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  5. John D. Lambris
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Correspondence to George Hajishengallis .

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Editors and Affiliations

  1. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    John D. Lambris

  2. Immunology, Genetics and Pathology, University of Uppsala, Uppsala, Sweden

    Kristina N. Ekdahl

  3. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Daniel Ricklin

  4. Immunology, Genetics and Pathology, University of Uppsala, Uppsala, Sweden

    Bo Nilsson

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Hajishengallis, G., Maekawa, T., Abe, T., Hajishengallis, E., Lambris, J.D. (2015). Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches. In: Lambris, J., Ekdahl, K., Ricklin, D., Nilsson, B. (eds) Immune Responses to Biosurfaces. Advances in Experimental Medicine and Biology, vol 865. Springer, Cham. https://doi.org/10.1007/978-3-319-18603-0_4

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