Distinct gut-derived lactic acid bacteria elicit divergent dendritic cell-mediated NK cell responses

Distinct gut-derived lactic acid bacteria elicit divergent dendritic cell-mediated NK cell responses
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DOI:
10.1093/intimm/dxm103
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发表时间:
2007-12-01
影响因子:
4.4
通讯作者:
Ferlazzo, Guido
Ferlazzo, Guido
中科院分区:
医学3区
文献类型:
--
作者:
Fink, Lisbeth N.;Zeuthen, Louise H.;Ferlazzo, Guido

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乳酸菌(LAB)在胃肠道中大量存在,在那里它们持续调节免疫系统。NK细胞被通过炎症刺激成熟的树突状细胞(DC)有效地激活,并且NK细胞存在于肠上皮和肠系膜淋巴结中,但不知道NK-DC相互作用如何受到主要非致病性LAB的影响。我们证明了暴露于不同肠源性LAB菌株的人DC一致地诱导自体NK细胞中的增殖、细胞毒性和活化标志物。相反,LAB菌株在诱导NK细胞产生DC依赖性IFN-γ的能力方面差异很大。这表明由肠道LAB刺激的DC可以扩大NK细胞池并增加其细胞毒性潜力。在DC中诱导高水平IL-12的特异性LAB可通过有效刺激NK细胞中IFN-γ的产生来促进1型应答的扩增。组合IFN-γ诱导性和非诱导性LAB完全消除DC介导的NK细胞的IFN-γ产生,因此调节NK细胞中IFN-γ产生的LAB可能是免疫应答的重要调节剂。
Lactic acid bacteria (LAB) are abundant in the gastrointestinal tract where they continuously regulate the immune system. NK cells are potently activated by dendritic cells (DCs) matured by inflammatory stimuli, and NK cells are present in the gut epithelium and in mesenteric lymph nodes, but it is not known how NK-DC interactions are affected by the predominantly non-pathogenic LAB. We demonstrate that human DCs exposed to different strains of gut-derived LAB consistently induce proliferation, cytotoxicity and activation markers in autologous NK cells. On the contrary, strains of LAB differ greatly in their ability to induce DC-dependent IFN-gamma production by NK cells. This suggests that DCs stimulated by gut LAB may expand the pool of NK cells and increase their cytotoxic potential. Specific LAB, inducing high levels of IL-12 in DCs, may promote amplification of a type-1 response via potent stimulation of IFN-gamma production in NK cells. Combining IFN-gamma-inducing and non-inducing LAB completely abrogates DC-mediated IFN-gamma production by NK cells, and therefore LAB modulating IFN-gamma production in NK cells may be important regulators of the immune response.