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Sci. Signal., 16 February 2010
Vol. 3, Issue 109, p. ra11
[DOI: 10.1126/scisignal.2000697]

RESEARCH ARTICLES

Editor's Summary

Disarming Crosstalk
The complement system is a key antimicrobial defense system and consists of a set of serum proteins that are converted to their active form by proteolytic cleavage. Many pathogens try to disable the complement system as part of their infection strategy. However, Porphyromonas gingivalis, an oral pathogen implicated in periodontitis and atherosclerosis, generates C5a, which is one of the active fragments of the fifth complement component and a macrophage chemoattractant. Wang et al. show that P. gingivalis evades the innate immune system by subverting communication between the C5a receptor (C5aR) and Toll-like receptor 2 (TLR2), another receptor that normally initiates antimicrobial responses. P. gingivalis and C5a combined to increase intracellular concentrations of cyclic adenosine monophosphate (cAMP), which suppressed macrophage function, and decrease production of nitric oxide, which enhanced P. gingivalis survival. These effects required crosstalk and association between C5aR and TLR2. Blockade of C5aR prevented the ability of P. gingivalis to evade the innate immune system and thus may be a therapeutic strategy in diseases involving this pathogen.

Citation: M. Wang, J. L. Krauss, H. Domon, K. B. Hosur, S. Liang, P. Magotti, M. Triantafilou, K. Triantafilou, J. D. Lambris, G. Hajishengallis, Microbial Hijacking of Complement–Toll-Like Receptor Crosstalk. Sci. Signal. 3, ra11 (2010).

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The C5a Receptor Impairs IL-12-Dependent Clearance of Porphyromonas gingivalis and Is Required for Induction of Periodontal Bone Loss.
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