C-Reactive Protein Promotes Inflammation through FcγR-Induced Glycolytic Reprogramming of Human Macrophages

J Immunol. 2019 Jul 1;203(1):225-235. doi: 10.4049/jimmunol.1900172. Epub 2019 May 22.


C-reactive protein (CRP) is an acute-phase protein produced in high quantities by the liver in response to infection and during chronic inflammatory disorders. Although CRP is known to facilitate the clearance of cell debris and bacteria by phagocytic cells, the role of CRP in additional immunological functions is less clear. This study shows that complexed CRP (phosphocholine [PC]:CRP) (formed by binding of CRP to PC moieties), but not soluble CRP, synergized with specific TLRs to posttranscriptionally amplify TNF, IL-1β, and IL-23 production by human inflammatory macrophages. We identified FcγRI and IIa as the main receptors responsible for initiating PC:CRP-induced inflammation. In addition, we identified the underlying mechanism, which depended on signaling through kinases Syk, PI3K, and AKT2, as well as glycolytic reprogramming. These data indicate that in humans, CRP is not only a marker but also a driver of inflammation by human macrophages. Therefore, although providing host defense against bacteria, PC:CRP-induced inflammation may also exacerbate pathology in the context of disorders such as atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis / immunology
  • C-Reactive Protein / chemistry
  • C-Reactive Protein / metabolism*
  • Cells, Cultured
  • Cellular Reprogramming
  • Cytokines / metabolism
  • Glycolysis
  • Humans
  • Inflammation / immunology*
  • Inflammation Mediators / metabolism
  • Liver / physiology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylcholine / chemistry
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, IgG / metabolism*
  • Signal Transduction
  • Syk Kinase / metabolism
  • Toll-Like Receptors / metabolism


  • Cytokines
  • FCGR1A protein, human
  • FCGR2A protein, human
  • Inflammation Mediators
  • Receptors, IgG
  • Toll-Like Receptors
  • Phosphorylcholine
  • C-Reactive Protein
  • Syk Kinase
  • Proto-Oncogene Proteins c-akt