Differential properties of CBA/J mononuclear phagocytes recovered from an inflammatory site and probed with two different species of Leishmania
Differential properties of CBA/J mononuclear phagocytes recovered from an inflammatory site and probed with two different species of Leishmania
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DOI：
10.1016/s1286-4579(03)00025-x
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发表时间：
2003-04-01
影响因子：
5.8
通讯作者：
Veras, PST
中科院分区：
文献类型：
--
作者：
Gomes, IN;Calabrich, AFD;Veras, PST
虽然CBA/J小鼠不能容忍亚马逊利什曼原虫驱动的致病过程，但它们很容易在利什曼原虫重大感染后痊愈。早期事件对利什曼原虫感染的结果至关重要，已知巨噬细胞(Mphi)在感染控制中起重要作用。在本研究中，我们研究了Mphi在推动CBA/J对亚马孙乳杆菌敏感性中的作用。我们进行了动力学研究，并比较了亚马孙乳杆菌和大乳杆菌感染Mphi的能力。两组6h感染率及寄生虫负荷率差异无统计学意义。相反，在12小时后，我们观察到亚马孙乳杆菌的感染率大约是主要乳杆菌感染Mphi的两倍。此外，加入重组人干扰素-γ可诱导一氧化氮(NO)的产生，但不能改变L感染亚马逊氏原虫的情况，但显著降低了主要乳杆菌的感染率。这种对主要乳杆菌感染的减少是一种肿瘤坏死因子-α依赖的机制，因为主要乳杆菌感染的Mphi表达的肿瘤坏死因子-α是亚马逊乳杆菌感染细胞的两倍，而抗肿瘤坏死因子-α逆转了干扰素-γ的作用。此外，重组人肿瘤坏死因子-α与干扰素-γ联合应用能显著降低感染亚马逊氏原虫的细胞百分率，但降低的程度不如主要感染原虫。尽管AMG比干扰素-γ处理的细胞产生更多的NO，但在干扰素-伽马和肿瘤坏死因子-α处理的细胞中加入AMG仅部分逆转了对主要乳杆菌的抑制，但不能逆转对亚马孙乳杆菌感染的抑制。因此，在这项研究中，我们证明了亚马孙钩端螺旋体既灭活又抵抗天然和干扰素-γ诱导的Mphi杀伤机制，表明寄生虫的性质及其与Mphi的相互作用可能决定免疫反应极化。(C)2003年版《爱思唯尔科学与医学》。版权所有。
While CBA/J mice fail to be permissive to Leishmania amazonensis-driven pathogenic processes, they heal easily following Leishmania major infection. The early-phase events are crucial to the outcome of Leishmania infection and it is known that macrophages (Mphi) are important in infection control. In the present study we investigated the role of Mphi in driving CBA/J susceptibility to L. amazonensis. We performed kinetic studies and compared the capacity of L. amazonensis and L. major to infect Mphi. There was no difference in percentages of infection or parasite burden for 6 h between the two groups. In contrast, after 12 h we observed that infection was about twice as high in L. amazonensis- than in L. major-infected Mphi. In addition, rIFN-gamma added to the cultures induced nitric oxide (NO) production, and did not modify L amazonensis infection, although the percentage of L. major infection was significantly reduced. This reduction in L. major infection is a TNF-alpha dependent mechanism as L. major-infected Mphi expressed twice as much TNF-alpha mRNA as L. amazonensis-infected cells, and anti-TNF-alpha reversed the IFN-gamma effect. Moreover, rTNF-alpha plus IFN-gamma were able to significantly reduce the percentage of L. amazonensis-infected cells but not to the same extent as in L. major infection. Despite having higher NO production than IFN-gamma-treated cells, AMG addition to IFN-gamma-plus TNF-alpha-treated cells only partially reversed the inhibition in L. major, but not in L. amazonensis infection. Thus, in this study, we demonstrated that L. amazonensis both inactivated and resisted innate and IFN-gamma-induced Mphi killing mechanisms, indicating that the nature of the parasite and its interaction with Mphi could determine immune response polarization. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.