Abstract
C-reactive protein (CRP) is an acute-phase protein in humans that is produced in high quantities by the liver upon infection and under inflammatory conditions. Although CRP is commonly used as a marker of inflammation, CRP can also directly contribute to inflammation by eliciting pro-inflammatory cytokine production by immune cells. Since CRP is highly elevated in serum under inflammatory conditions, we have studied the CRP-induced cytokine profile of human monocytes, one of the main innate immune cell populations in blood. We identified that CRP is relatively unique in its capacity to induce production of the pro-inflammatory cytokine IL-23, which was in stark contrast to a wide panel of pattern recognition receptor (PRR) ligands. We show that CRP-induced IL-23 production was mediated at the level of gene transcription, since CRP particularly promoted gene transcription of IL23A (encoding IL-23p19) instead of IL12A (encoding IL-12p35), while PRR ligands induce the opposite response. Interestingly, when CRP stimulation was combined with PRR ligand stimulation, as for example, occurs in the context of sepsis, IL-23 production by monocytes was strongly reduced. Combined, these data identify CRP as a unique individual ligand to induce IL-23 production by monocytes, which may contribute to shaping systemic immune responses under inflammatory conditions.
Highlights
C-reactive protein (CRP) belongs to the family of pentraxins and is an acute phase protein in humans, meaning that it is rapidly up-regulated in serum under inflammatory conditions
Since CRP is highly elevated in serum under inflammatory conditions, we have set out to investigate the cytokine profile that is induced by human monocytes, one of the main innate immune cell populations in blood
When comparing CRP and pattern recognition receptor (PRR) ligands, we identified that CRP inwe stimulated monocytes with CRP and a variety of other PRR ligands and compared duced relatively higher levels of IL23A, while PRR ligands Poly I:C and LPS induced relmRNA expression of the two IL-23 subunits, IL-23p19 and atively higherIL-12p40 levels
Summary
C-reactive protein (CRP) belongs to the family of pentraxins and is an acute phase protein in humans, meaning that it is rapidly up-regulated in serum under inflammatory conditions. CRP is predominantly produced by the liver in response to IL-6, following injury, infection or trauma [1]. Baseline serum concentrations of CRP are less than 3 mg/L, but this level may increase to 500 mg/L within 24–48 h from the onset of infection or inflammation [1,2]. There is growing evidence that CRP plays an active role in inflammatory processes and host defense responses. CRP can bind to various pathogens, mainly bacteria, and to damaged or dying cells to promote their phagocytosis by human leukocytes. Several studies have shown that CRP can provide protection against multiple bacteria, including
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