TY - JOUR
T1 - Macrophage subset sensitivity to endotoxin tolerisation by Porphyromonas gingivalis.
AU - Foey, Andrew D.
AU - Crean, St John
PY - 2013
Y1 - 2013
N2 - Macrophages (MΦs) determine oral mucosal responses; mediating tolerance to commensal microbes and food whilst maintaining the capacity to activate immune defences to pathogens. MΦ responses are determined by both differentiation and activation stimuli, giving rise to two distinct subsets; pro-inflammatory M1- and anti-inflammatory/regulatory M2- MΦs. M2-like subsets predominate tolerance induction whereas M1 MΦs predominate in inflammatory pathologies, mediating destructive inflammatory mechanisms, such as those in chronic P.gingivalis (PG) periodontal infection. MΦ responses can be suppressed to benefit either the host or the pathogen. Chronic stimulation by bacterial pathogen associated molecular patterns (PAMPs), such as LPS, is well established to induce tolerance. The aim of this study was to investigate the susceptibility of MΦ subsets to suppression by P. gingivalis. CD14(hi) and CD14(lo) 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 pre-treated with heat-killed PG (HKPG) and PG-LPS prior to stimulation by bacterial PAMPs. Modulation of inflammation was measured by TNFα, IL-1β, IL-6, IL-10 ELISA and NFκB activation by reporter gene assay. HKPG and PG-LPS differentially suppress PAMP-induced TNFα, IL-6 and IL-10 but fail to suppress IL-1β expression in M1 and M2 MΦs. In addition, P.gingivalis suppressed NFκB activation in CD14(lo) and CD14(hi) M2 regulatory MΦs and CD14(lo) M1 MΦs whereas CD14(hi) M1 pro-inflammatory MΦs were refractory to suppression. In conclusion, P.gingivalis selectively tolerises regulatory M2 MΦs with little effect on pro-inflammatory CD14(hi) M1 MΦs; differential suppression facilitating immunopathology at the expense of immunity.
AB - Macrophages (MΦs) determine oral mucosal responses; mediating tolerance to commensal microbes and food whilst maintaining the capacity to activate immune defences to pathogens. MΦ responses are determined by both differentiation and activation stimuli, giving rise to two distinct subsets; pro-inflammatory M1- and anti-inflammatory/regulatory M2- MΦs. M2-like subsets predominate tolerance induction whereas M1 MΦs predominate in inflammatory pathologies, mediating destructive inflammatory mechanisms, such as those in chronic P.gingivalis (PG) periodontal infection. MΦ responses can be suppressed to benefit either the host or the pathogen. Chronic stimulation by bacterial pathogen associated molecular patterns (PAMPs), such as LPS, is well established to induce tolerance. The aim of this study was to investigate the susceptibility of MΦ subsets to suppression by P. gingivalis. CD14(hi) and CD14(lo) 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 pre-treated with heat-killed PG (HKPG) and PG-LPS prior to stimulation by bacterial PAMPs. Modulation of inflammation was measured by TNFα, IL-1β, IL-6, IL-10 ELISA and NFκB activation by reporter gene assay. HKPG and PG-LPS differentially suppress PAMP-induced TNFα, IL-6 and IL-10 but fail to suppress IL-1β expression in M1 and M2 MΦs. In addition, P.gingivalis suppressed NFκB activation in CD14(lo) and CD14(hi) M2 regulatory MΦs and CD14(lo) M1 MΦs whereas CD14(hi) M1 pro-inflammatory MΦs were refractory to suppression. In conclusion, P.gingivalis selectively tolerises regulatory M2 MΦs with little effect on pro-inflammatory CD14(hi) M1 MΦs; differential suppression facilitating immunopathology at the expense of immunity.
KW - Cell Line
KW - Humans
KW - Immune Tolerance
KW - Lipopolysaccharide Receptors
KW - Lipopolysaccharides
KW - Macrophages
KW - NF-kappa B
KW - Porphyromonas gingivalis
UR - https://pearl.plymouth.ac.uk/context/bhs-research/article/1010/viewcontent/Macrophage_20subset_20sensitivity_20to_20endotoxin_20tolerisation_20by_20Porphyromonas_20gingivalis.pdf
U2 - 10.1371/journal.pone.0067955
DO - 10.1371/journal.pone.0067955
M3 - Article
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 7
ER -