Phagocytosis of Borrelia burgdorferi and Treponema pallidum potentiates innate immune activation and induces gamma interferon production
Phagocytosis of Borrelia burgdorferi and Treponema pallidum potentiates innate immune activation and induces gamma interferon production
复制标题
DOI：
10.1128/iai.01666-06
复制
发表时间：
2007-04-01
影响因子：
3.1
通讯作者：
Radolf, Justin D.
中科院分区：
文献类型：
--
作者：
Moore, Meagan W.;Cruz, Adriana R.;Radolf, Justin D.
我们研究了活的和裂解的螺旋体与先天免疫细胞的相互作用。THP-1单核细胞样细胞被活伯氏疏螺旋体和B激活到相当的程度。burgdorferi和梅毒螺旋体裂解物，但活T.苍白球因为THP-1细胞很难内化活的螺旋体，我们转向了离体外周血单核细胞系统，该系统将更密切地反映实际感染期间发生的螺旋体-单核吞噬细胞相互作用。在该系统中，B.与疏螺旋体裂解物或T.苍白球，只有B。burgdorferi从NK细胞引发γ干扰素（IFN-γ）。B。burgdorferi被单核细胞吞噬，而T.苍白球则无，提示对肝B. Burgdorferi是由于吞噬有机体。当细胞松弛素D阻断肝细胞吞噬B时。burgdorferi，细胞因子产生降低至与B诱导的水平相当的水平。Burgdorferi裂解物，而IFN-γ应答被完全消除。在人梅毒血清存在下，T.苍白球被有效地内化并引发类似于用活B观察到的反应。包括NK细胞产生IFN-γ。单核细胞的消耗揭示了它们是炎性细胞因子的主要来源，而树突状细胞（DC）指导先天淋巴细胞产生IFN-γ。因此，活螺旋体的吞噬作用启动单核细胞和DC中的细胞活化程序，所述细胞活化程序在定性和定量上不同于由富含脂蛋白的裂解物在细胞表面诱导的那些。菲里对T苍白球似乎可以用B的成功的更大的刺激能力来解释。burgdorferi识别和吞噬B。和T.苍白球，以避免检测和吸收凭借其裸露的外膜，而不是在表面脂蛋白表达的差异。
We examined the interactions of live and lysed spirochetes with innate immune cells. THP-1 monocytoid cells were activated to comparable extents by live Borrelia burgdorferi and by B. burgdorferi and Treponema pallidum lysates but were poorly activated by live T. pallidum. Because THP-1 cells poorly internalized live spirochetes, we turned to an ex vivo peripheral blood mononuclear cell system that would more closely reflect spirochete-mononuclear phagocyte interactions that occur during actual infection. In this system, B. burgdorferi induced significantly greater monocyte activation and inflammatory cytokine production than did borrelial lysates or T. pallidum, and only B. burgdorferi elicited gamma interferon (IFN-gamma) from NK cells. B. burgdorferi was phagocytosed avidly by monocytes, while T. pallidum was not, suggesting that the enhanced response to live B. burgdorferi was due to phagocytosis of the organism. When cytochalasin D was used to block phagocytosis of live B. burgdorferi, cytokine production decreased to levels comparable to those induced by B. burgdorferi lysates, while the IFN-gamma response was abrogated altogether. In the presence of human syphilitic serum, T. pallidum was efficiently internalized and initiated responses resembling those observed with live B. burgdorferi, including the production of IFN-gamma by NK cells. Depletion of monocytes revealed that they were the primary source of inflammatory cytokines, while dendritic cells (DCs) directed IFN-gamma production from innate lymphocytes. Thus, phagocytosis of live spirochetes initiates cell activation programs in monocytes and DCs that differ qualitatively and quantitatively from those induced at the cell surface by lipoprotein-enriched lysates. The fieri versus T. pallidum appears to be explained by the successful greater stimulatory capacity of B. burgdorferi recognition and phagocytosis of B. burgdorferi by host cells and the ability of T. pallidum to avoid detection and uptake by virtue of its denuded outer membrane rather than by differences in surface lipoprotein expression.