Macrophage subset sensitivity to endotoxin tolerisation by Porphyromonas gingivalis.
Macrophage subset sensitivity to endotoxin tolerisation by Porphyromonas gingivalis.
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DOI：
10.1371/journal.pone.0067955
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Crean S
中科院分区：
文献类型：
--
作者：
Foey AD;Crean S
巨噬细胞（MΦs）决定口腔粘膜反应;介导对口腔微生物和食物的耐受性，同时保持激活对病原体的免疫防御的能力。MΦ反应由分化和活化刺激决定，产生两个不同的子集;促炎性M1-和抗炎/调节性M2- MΦ。M2样亚群主导耐受诱导，而M1 MΦ在炎症病理中占主导地位，介导破坏性炎症机制，例如慢性牙龈卟啉单胞菌（PG）牙周感染中的那些。MΦ反应可以被抑制以有利于宿主或病原体。细菌病原体相关分子模式（PAMP）（例如LPS）的慢性刺激被充分确立以诱导耐受性。本研究的目的是研究MΦ亚群对牙龈卟啉单胞菌抑制的敏感性。通过分别用PMA和维生素D3分化，从THP-1单核细胞系体外产生CD 14 hi和CD 14 lo M1-和M2-样MΦ。在用细菌PAMP刺激之前，用热灭活的PG（HKPG）和PG-LPS预处理MΦ亚群。通过ELISA检测TNFα、IL-1β、IL-6、IL-10对炎症的调节作用，通过报告基因检测NFκB活化。在M1和M2 MΦ中，HKPG和PG-LPS不同地抑制PAMP诱导的TNFα、IL-6和IL-10的表达，但不能抑制IL-1β的表达。此外，牙龈卟啉单胞菌抑制CD 14 lo和CD 14 hi M2调节性MΦs和CD 14 lo M1 MΦs中的NFκB活化，而CD 14 hi M1促炎性MΦs难以抑制。总之，牙龈卟啉单胞菌选择性地耐受调节性M2 MΦ，对促炎性CD 14 hi M1 MΦ几乎没有影响;差异抑制以免疫为代价促进免疫病理学。
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. CD14hi and CD14lo 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 CD14lo and CD14hi M2 regulatory MΦs and CD14lo M1 MΦs whereas CD14hi M1 pro-inflammatory MΦs were refractory to suppression. In conclusion, P.gingivalis selectively tolerises regulatory M2 MΦs with little effect on pro-inflammatory CD14hi M1 MΦs; differential suppression facilitating immunopathology at the expense of immunity.
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