C-reactive protein collaborates with plasma lectins to boost immune response against bacteria.
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.
Ng
Patricia M L
PM
Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore.
Le Saux
Agnès
A
Lee
Chia M
CM
Tan
Nguan S
NS
Lu
Jinhua
J
Thiel
Steffen
S
Ho
Bow
B
Ding
Jeak L
JL
D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000187:drug effects / Q000276:immunology*; D001798:Blood Proteins / Q000378:metabolism; D002097:C-Reactive Protein / Q000737:chemistry / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry; D003167:Complement Activation / Q000187:drug effects; D037582:Complement Pathway, Mannose-Binding Lectin / Q000187:drug effects / Q000276:immunology; D006458:Hemolymph / Q000737:chemistry / Q000187:drug effects; D006737:Horseshoe Crabs / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007109:Immunity / Q000187:drug effects / Q000276:immunology*; D037102:Lectins / Q000097:blood* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008954:Models, Biological; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000737:chemistry; D033902:Periplasmic Binding Proteins / Q000737:chemistry; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D020239:Receptor Cross-Talk / Q000187:drug effects; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D019779:Salmonella enterica / Q000187:drug effects / Q000276:immunology; D000097604:Ficolins
D001798:Blood Proteins; D002097:C-Reactive Protein; D002135:Calcium-Binding Proteins; D037102:Lectins; D008070:Lipopolysaccharides; D009004:Monosaccharide Transport Proteins; D033902:Periplasmic Binding Proteins; D051192:Receptors, Pattern Recognition; D000097604:Ficolins; C023550:galactose-binding protein