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


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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J. Immunol. 192, 2857-2864
   Abstract »    Full Text »    PDF »
Inflammatory Responses Induced by Lipopolysaccharide Are Amplified in Primary Human Monocytes but Suppressed in Macrophages by Complement Protein C5a.
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J. Immunol. 191, 4308-4316
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Suppression of T-Cell Chemokines by Porphyromonas gingivalis.
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   Abstract »    Full Text »    PDF »
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J. Immunol. 189, 5442-5448
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C5a Receptor-Dependent Cell Activation by Physiological Concentrations of Desarginated C5a: Insights from a Novel Label-Free Cellular Assay.
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Journal of Dental Research 91, 816-820
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A Metalloproteinase Karilysin Present in the Majority of Tannerella forsythia Isolates Inhibits All Pathways of the Complement System.
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J. Immunol. 188, 2338-2349
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Journal of Dental Research 90, 417-427
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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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J. Immunol. 186, 869-877
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Destructive and Protective Roles of Cytokines in Periodontitis: A Re-appraisal from Host Defense and Tissue Destruction Viewpoints.
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"Complementing" Toll Signaling.
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Science Signaling Podcast: 16 February 2010.
G. Hajishengallis and A. M. VanHook (2010)
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