The Acute-Phase Reactant C-Reactive Protein Binds to Phosphorylcholine-ExpressingNeisseria meningitidisand Increases Uptake by Human Phagocytes

Abstract

Neisseria meningitidisis a global cause of meningitis and septicemia. Immunity toN. meningitidisinvolves both innate and specific mechanisms with killing by serum bactericidal activity and phagocytic cells. C-reactive protein (CRP) is an acute-phase serum protein that has been shown to help protect the host from several bacterial pathogens, which it recognizes by binding to phosphorylcholine (PC) on their surfaces. PathogenicNeisseriaspecies can exhibit phase-variable PC modification on type 1 and 2 pili. We have shown that CRP can bind to piliated meningococci in a classical calcium-dependent manner. The binding of CRP to the meningococcus was concentration dependent, of low affinity, and specific for PC. CRP appears to act as an opsonin forN. meningitidis, as CRP-opsonized bacteria showed increased uptake by human macrophages and neutrophils. Further investigation into the downstream effects of CRP-boundN. meningitidismay lead us to a better understanding of meningococcal infection and help direct more effective therapeutic interventions.