Porphyromonas gingivalis-stimulated macrophage subsets exhibit differential induction and responsiveness to interleukin-10.
OBJECTIVE
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.


CONCLUSIONS
P.gingivalis selectively tolerises regulatory M2 Mϕs with little effect on pro-inflammatory M1 Mϕs; differential suppression facilitating immunopathology at the expense of immunity.
School of Biomedical & Healthcare Sciences, Plymouth University Peninsula Schools of Medicine and Dentistry, Drake Circus, Plymouth PL4 8AA, United Kingdom. Electronic address: andrew.foey@plymouth.ac.uk.
Andrew D
AD
Foey
School of Biomedical & Healthcare Sciences, Plymouth University Peninsula Schools of Medicine and Dentistry, Drake Circus, Plymouth PL4 8AA, United Kingdom.
Neama
N
Habil
School of Biomedical & Healthcare Sciences, Plymouth University Peninsula Schools of Medicine and Dentistry, Drake Circus, Plymouth PL4 8AA, United Kingdom.
Khalid
K
Al-Shaghdali
Faculty of Health & Social Work, University of Central Lancashire, Preston, Lancs, PR1 2HE, United Kingdom.
StJohn
S
Crean
D016866:Bacteroidaceae Infections / Q000276:immunology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D054884:Host-Pathogen Interactions; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D009000:Monocytes / Q000276:immunology; D009061:Mouth Mucosa / Q000276:immunology / Q000382:microbiology*; D000069452:Pathogen-Associated Molecular Pattern Molecules / Q000276:immunology / Q000378:metabolism; D010518:Periodontitis / Q000276:immunology; D016966:Porphyromonas gingivalis / Q000276:immunology* / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014807:Vitamin D / Q000494:pharmacology
C508609:IL10 protein, human; D008070:Lipopolysaccharides; D000069452:Pathogen-Associated Molecular Pattern Molecules; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D014807:Vitamin D
Endotoxin tolerance; Inflammation; Interleukin-10; Macrophage; Periodontitis