Porphyromonas gingivalis-stimulated macrophage subsets exhibit differential induction and responsiveness to interleukin-10. (January 2017)

• Record Type: Journal Article
• Authors: Foey, Andrew D.; Habil, Neama; Al-Shaghdali, Khalid; Crean, StJohn
• Is Part Of: Archives of oral biology. Volume 73(2017)
• Page Start: 282
• Page End: 288
• Publication Date: 2017-01
• Subjects: Mϕs macrophages -- IL-10 interleukin-10 -- IL-10R interleukin-10 Receptor -- TNFα tumour necrosis factor-α -- CP chronic periodontitis -- PG-LPS porphyromonas gingivalis lipopolysaccharide -- TLR toll-like receptor -- ET endotoxin tolerance -- STAT-3 signal transducer and activation of transcription-3 -- NFκB nuclear factor-kappa B -- SOCS-3 suppressor of cytokine signalling-3 -- PAMPs pathogen associated molecular patterns; Periodontitis -- Macrophage -- Inflammation -- Endotoxin tolerance -- Interleukin-10; Mouth -- Periodicals; Mouth -- Diseases -- Periodicals; Dentistry -- Periodicals; Electronic journals; 617.6005
• DOI: 10.1016/j.archoralbio.2016.10.029
• Languages: English
• ISSNs: 0003-9969

Abstract

Highlights: PG-LPS differentially induces macrophage subset IL-10 production. IL-10 suppresses PG-LPS induced M2 macrophage TNFα secretion. M1 pro-inflammatory macrophages are refractory to IL-10 activity. IL-10 receptor subunit expression is comparable between M1 and M2 macrophages. STAT-3 activation accounts for difference in Mϕ subset responses to IL-10. Abstract: Objectives: Oral mucosal macrophages (Mϕs) determine immune responses; maintaining tolerance whilst retaining the capacity to activate defences against pathogens. Mϕ responses are determined by two distinct subsets; pro-inflammatory M1- and anti-inflammatory/regulatory M2-Mϕs. Tolerance induction is driven by M2 Mϕs, whereas M1-like Mϕs predominate in inflammation, such as that exhibited in chronic Porphyromonas gingivalis (PG) periodontal infection. Mϕ responses can be suppressed to benefit either the host or the pathogen. Chronic stimulation by pathogen associated molecular patterns (PAMPs), such as LPS, is well established to induce tolerance. The aim of this study was to investigate the P. gingivalis -driven induction of and responsiveness to the suppressive, anti-inflammatory cytokine, IL-10, by Mϕ subsets. Methods: M1- and M2-like Mϕs were generated in vitro from the THP-1 monocyte cell line by differentiation with PMA and Vitamin D3, respectively. Mϕ subsets were stimulated by PG-LPS in the presence or absence of IL-10. Results: PG-LPS differentially induced IL-10 secretion and endogenous IL-10 activity in M1- and M2-like subsets. In addition, these subsets exhibited differential sensitivity to IL-10-mediated suppression of TNFα, where M2 Mϕs where sensitive to IL-10 and M1 Mϕs were refractory to suppression. In addition, this differential responsiveness to IL-10 was independent of IL-10-binding and expression of the IL-10 receptor signal transducing subunit, IL-10Rβ, but was in fact dependent on activation of STAT-3. Conclusion: P.gingivalis selectively tolerises regulatory M2 Mϕs with little effect on pro-inflammatory M1 Mϕs; differential suppression facilitating immunopathology at the expense of immunity.