Differential interaction of dendritic cells with Rickettsia conorii:: Impact on host susceptibility to murine spotted fever rickettsiosis
Differential interaction of dendritic cells with Rickettsia conorii:: Impact on host susceptibility to murine spotted fever rickettsiosis
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DOI：
10.1128/iai.00007-07
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发表时间：
2007-06-01
影响因子：
3.1
通讯作者：
Walker, David H.
中科院分区：
文献类型：
--
作者：
Fang, Rong;Ismail, Nahed;Walker, David H.
斑点热群立克次体病正在不断出现和重新出现，其中一些甚至危及生命。为了了解树突状细胞 (DC) 如何促进宿主对立克次体疾病的抵抗或易感性，我们首先表征了立克次体与来自耐药 C57BL/6 (B6) 和易感 C3H/HeN (C3H) 小鼠的骨髓来源 DC (BMDC) 的体外相互作用。与内皮细胞内的完全胞质定位相反，立克次体有效地进入并定位于两种小鼠品系的BMI)C的吞噬体和胞质中。与 C3H 小鼠相比，来自耐药小鼠的康氏立克次体感染的 BMI)C 具有更高的细菌载量。根据经典主要组织相容性复合体 (MHC) 和共刺激分子表达上调判断，R. conorii 感染诱导两种小鼠品系的 BMDC 成熟。与C3H对应物相比，B6 BMI)Cs在立克次体感染后表现出更高的MHC II类表达水平和更高的白细胞介素12 (IL-12) p40产量，并且在启动幼稚CD4(+) T细胞产生γ干扰素方面更有效。体外 DC 感染和 T 细胞启动研究表明，C3H 小鼠中 CD4(+) T 细胞活化延迟并抑制 Th1/Th2 细胞发育。 C3H 小鼠中观察到的抑制性 CD4(+) T 细胞反应与在 IL-2 存在下同基因 R. conorii 感染的 BMI)C 所促进的高频率 Foxp3(+) T 调节细胞相关。这些数据表明，立克次体可以靶向树突状细胞，在耐药宿主中刺激保护性 1I 型反应，但在易感宿主中抑制适应性免疫。
Spotted fever group rickettsioses are emerging and reemerging infectious diseases, some of which are life-threatening. In order to understand how dendritic cells (DCs) contribute to the host resistance or susceptibility to rickettsial diseases, we first characterized the in vitro interaction of rickettsiae with bone marrow-derived DCs (BMDCs) from resistant C57BL/6 (B6) and susceptible C3H/HeN (C3H) mice. In contrast to the exclusively cytosolic localization within endothelial cells, rickettsiae efficiently entered and localized in both phagosomes and cytosol of BMI)Cs from both mouse strains. Rickettsia conorii-infected BMI)Cs from resistant mice harbored higher bacterial loads compared to C3H mice. R. conorii infection induced maturation of BMDCs from both mouse strains as judged by upregulated expression of classical major histocompatibility complex (MHC) and costimulatory molecules. Compared to C3H counterparts, B6 BMI)Cs exhibited higher expression levels of MHC class II and higher interleukin-12 (IL-12) p40 production upon rickettsial infection and were more potent in priming naive CD4(+) T cells to produce gamma interferon. In vitro DC infection and T-cell priming studies suggested a delayed CD4(+) T-cell activation and suppressed Th1/Th2 cell development in C3H mice. The suppressive CD4(+) T-cell responses seen in C3H mice were associated with a high frequency of Foxp3(+) T regulatory cells promoted by syngeneic R. conorii-infected BMI)Cs in the presence of IL-2. These data suggest that rickettsiae can target DCs to stimulate a protective type 1I response in resistant hosts but suppressive adaptive immunity in susceptible hosts.