Secondary lymphoid organ homing phenotype of human myeloid dendritic cells disrupted by an intracellular oral pathogen.
Secondary lymphoid organ homing phenotype of human myeloid dendritic cells disrupted by an intracellular oral pathogen.
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被细胞内口腔病原体破坏的人骨髓树突状细胞的次级淋巴器官归巢表型。
DOI：
10.1128/iai.01157-13
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发表时间：
2014
影响因子：
3.1
通讯作者：
Cutler,ChristopherW
中科院分区：
文献类型：
--
作者：
Miles,Brodie;Zakhary,Ibrahim;El-Awady,Ahmed;Scisci,Elizabeth;Carrion,Julio;O'Neill,JohnC;Rawlings,Aaron;Stern,JKobi;Susin,Cristiano;Cutler,ChristopherW
几种细胞内病原体，包括慢性牙周炎的关键病原体，牙龈卟啉单胞菌，感染血液髓系树突状细胞(MDCs)。这种感染导致病原体传播到远处的炎症部位(即病原体贩运)。趋化因子-趋化因子受体表达的改变有助于这种病原体的转运功能，特别是对人类新生血管的部位，目前尚不清楚。为了研究这一点，我们利用体外培养的人单核细胞来源的DC(MoDC)和原代内皮细胞，结合来自慢性牙周炎患者和健康对照组的体内分离的血MDCs和血清。我们的结果，使用牙龈假单胞菌的条件菌毛突变体，表明牙龈假单胞菌感染MoDC诱导了血管生成的迁移特征。这种表达被MoDC上的DC-SIGN和牙龈假单胞菌上的微小MFA-1菌毛所增强，并被CXCR4的强劲上调所证明，但不是次级淋巴器官(SLO)归巢的CCR7。趋化因子对SLO归巢能力的破坏与CXCR4和CCR7的表面表达密切相关，并与MoDC通过内皮单分子层的定向迁移一致。体外分离的慢性牙周炎患者血液中的MDCs，但不是健康对照组，表达了类似的迁移特征；此外，慢性牙周炎患者的血清表达了高水平的CXCL12。总体而言，我们得出结论，牙龈假单胞菌通过重新编程趋化因子受体，从而扰乱SLO的归巢，同时推动向炎症血管部位的迁移，积极地“征用”DC。
Several intracellular pathogens, including a key etiological agent of chronic periodontitis, Porphyromonas gingivalis, infect blood myeloid dendritic cells (mDCs). This infection results in pathogen dissemination to distant inflammatory sites (i.e., pathogen trafficking). The alteration in chemokine-chemokine receptor expression that contributes to this pathogen trafficking function, particularly toward sites of neovascularization in humans, is unclear. To investigate this, we utilized human monocyte-derived DCs (MoDCs) and primary endothelial cellsin vitro, combined withex vivo-isolated blood mDCs and serum from chronic periodontitis subjects and healthy controls. Our results, using conditional fimbria mutants of P. gingivalis, show that P. gingivalis infection of MoDCs induces an angiogenic migratory profile. This profile is enhanced by expression of DC-SIGN on MoDCs and minor mfa-1 fimbriae on P. gingivalis and is evidenced by robust upregulation of CXCR4, but not secondary lymphoid organ (SLO)-homing CCR7. This disruption of SLO-homing capacity in response to respective chemokines closely matches surface expression of CXCR4 and CCR7 and is consistent with directed MoDC migration through an endothelial monolayer.Ex vivo-isolated mDCs from the blood of chronic periodontitis subjects, but not healthy controls, expressed a similar migratory profile; moreover, sera from chronic periodontitis subjects expressed elevated levels of CXCL12. Overall, we conclude that P. gingivalis actively “commandeers” DCs by reprogramming the chemokine receptor profile, thus disrupting SLO homing, while driving migration toward inflammatory vascular sites.