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  • The EMBO Journal (2007) 26, 3431 - 3440
  • doi:10.1038/sj.emboj.7601762

Published online: 21 June 2007

C-reactive protein collaborates with plasma lectins to boost immune response against bacteria

Patricia ML Ng1, Agnès Le Saux1, Chia M Lee1, Nguan S Tan2, Jinhua Lu3, Steffen Thiel4, Bow Ho3,a and Jeak L Ding1

  1. Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore
  2. School of Biological Sciences, Nanyang Technological University, Singapore
  3. Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  4. Department of Medical Microbiology and Immunology, Wilhelm Meyers Allé, Bartholin Building, University of Aarhus, Aarhus, Denmark

Correspondence to:

Jeak L Ding, Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore. Tel.: 65 6516 2776; Fax: 65 6779 2486; E-mail: dbsdjl@nus.edu.sg

aThese authors contributed equally to this work

Received 23 November 2006; Accepted 24 May 2007

Although human C-reactive protein (CRP) becomes upregulated during septicemia, its role remains unclear, since purified CRP showed no binding to many common pathogens. Contrary to previous findings, we show that purified human CRP (hCRP) binds to Salmonella enterica, and that binding is enhanced in the presence of plasma factors. In the horseshoe crab, Carcinoscorpius rotundicauda, CRP is a major hemolymph protein. Incubation of hemolymph with a range of bacteria resulted in CRP binding to all the bacteria tested. Lipopolysaccharide-affinity chromatography of the hemolymph co-purified CRP, galactose-binding protein (GBP) and carcinolectin-5 (CL5). Yeast two-hybrid and pull-down assays suggested that these pattern recognition receptors (PRRs) form pathogen recognition complexes. We show the conservation of PRR crosstalk in humans, whereby hCRP interacts with ficolin (CL5 homologue). This interaction stabilizes CRP binding to bacteria and activates the lectin-mediated complement pathway. We propose that CRP does not act alone but collaborates with other plasma PRRs to form stable pathogen recognition complexes when targeting a wide range of bacteria for destruction.

  • Keywords:

    • C-reactive protein,
    • complement,
    • crosstalk,
    • ficolin,
    • inflammation