Human dendritic cells respond to Porphyromonas gingivalis LPS by promoting a Th2 effector response in vitro

Human dendritic cells respond to Porphyromonas gingivalis LPS by promoting a Th2 effector response in vitro
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DOI:
10.1002/eji.200324392
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发表时间:
2003-11-01
影响因子:
5.4
通讯作者:
Cutler, CW
Cutler, CW
中科院分区:
医学3区
文献类型:
--
作者:
Jotwani, R;Pulendran, B;Cutler, CW

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Understanding how mucosal pathogens modulate the immune response may facilitate the development of vaccines for disparate human diseases. In the present study, human monocyte-derived DC (MDDC) were pulsed with LIPS of the oral pathogen Porphyromonas gingivalis and Escherichia coli 25922 and analyzed for: (i) production of Th-biasing/inflammatory cytokines; (ii) maturation/costimulatory molecules; and (iii) induction of allogeneic CD4(+) and naive CD45RA(+) T cell proliferation and release of Th1 or Th2 cytokines. We show that E coli LPS-pulsed MDDC released Th1-biasing cytokines - consisting of high levels of IL-12 p70, IFN-gamma-inducible protein 10 (IP-10) - but also TNF-alpha, IL-10, IL-6 and IL-1beta. In contrast, no IL-12 p70 or IP-10, and lower levels of TNF-alpha and IL-10 were induced by P. gingivalis LPS. These differences were sustained at LIPS doses that yielded nearly equivalent maturation of MDDC; moreover the T cell response was consistent: E coli LIPS-pulsed MDDC induced higher T cell proliferation, and T cells released more IFN-gamma and IL-2, but less IL-5 than T cells co-cultured with P. gingivalis LIPS pulsed-MDDC. IL-13 was secreted by naive CD45RA(+)CD45RO(-)CD4(+)T cells in response to P. gingivalisLPS-pulsed MDDC. These results suggest that human MDDC can be polarized by LIPS from the mucosal pathogen P. gingivalis to induce a Th2 effector response in vitro.