Multiple host defense defects in failure of C57BL/6 ep/ep (pale ear) mice to resolve visceral Leishmania donovani infection.
Multiple host defense defects in failure of C57BL/6 ep/ep (pale ear) mice to resolve visceral Leishmania donovani infection.
复制标题
C57BL/6 ep/ep（苍耳）小鼠未能解决内脏杜氏利什曼原虫感染时存在多种宿主防御缺陷。
DOI：
10.1128/iai.64.1.161-166.1996
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发表时间：
1996
影响因子：
3.1
通讯作者：
Stoeckle,MY
中科院分区：
文献类型：
--
作者：
Murray,HW;Hariprashad,J;McDermott,DF;Stoeckle,MY
无菌C57BL/L ep/ep （pale ear [PE]）小鼠能阻断细胞内多诺瓦利什曼原虫的内脏复制，但不能有效解决感染。先前的一项研究在这些小鼠中发现了组织肉芽肿形成的孤立缺陷；CD4+和CD8+细胞数量、γ干扰素（ifn - γ）的产生以及巨噬细胞的体外抗菌活性均未受影响。这里报道的新的体内研究结果表明，一种相当复杂的免疫缺陷，有证据表明(i)正常C57BL/6脾细胞移植后对L. donovani的控制增强，（ii）由白细胞介素-4 （IL-4）介导的部分抑制Th2细胞相关反应，但不被CD4+细胞消耗逆转，（iii）对内源性Th1细胞淋巴因子（ifn - γ和IL-2）没有反应，但保留了对内源性肿瘤坏死因子α的反应。（iv）对外源性抗利什曼细胞因子（ifn - γ、IL-2、IL-12和粒细胞-巨噬细胞集落刺激因子[GM-CSF]）治疗缺乏反应，不能通过C57BL/6脾细胞转移纠正；(v)对锑化疗反应不足。C57BL/6脾细胞移植或抗il -4治疗均不能纠正肝肉芽肿形成缺陷。虽然用IL-2和GM-CSF处理可以改变组织反应并诱导选定的效应细胞包裹组织巨噬细胞，但没有抗利什曼原虫活性。总之，这些观察结果表明，PE小鼠解决内脏多诺氏乳杆菌感染的失败可能代表了多种次优免疫反应和/或部分缺陷的表达，可能涉及t细胞功能障碍、Th2细胞反应和靶细胞（巨噬细胞）低反应的组合。
Euthymic C57BL/L ep/ep (pale ear [PE]) mice halt the visceral replication of intracellular Leishmania donovani but fail to properly resolve infection. A previous study identified an isolated defect in tissue granuloma formation in these mice; CD4+ and CD8+ cell number, gamma interferon (IFN-gamma) production, and macrophage antimicrobial activity in vitro were all intact. New in vivo results reported here suggest a considerably more complex immune defect, with evidence indicating (i) enhanced control over L. donovani after transfer of normal C57BL/6 spleen cells, (ii) a partially suppressive Th2 cell-associated response mediated by interleukin-4 (IL-4) but not reversed by CD4+ cell depletion, (iii) absent responses to endogenous Th1 cell lymphokines (IFN-gamma and IL-2) but preserved responsiveness to endogenous tumor necrosis factor alpha, (iv) absent responses to exogenous treatment with recognized antileishmanial cytokines (IFN-gamma, IL-2, IL-12, and granulocyte-macrophage colony-stimulating factor [GM-CSF]) not corrected by transfer of C57BL/6 spleen cells, and (v) a deficient response to antimony chemotherapy. Defective hepatic granuloma formation was not corrected by transfer of C57BL/6 spleen cells or by anti-IL-4 administration. While treatment with IL-2 and GM-CSF modified the tissue reaction and induced selected effector cells to encase tissue macrophages, no antileishmanial activity resulted. Together, these observations suggest that the failure of PE mice to resolve visceral L. donovani infection likely represents expression of multiple suboptimal immune responses and/or partial defects, probably involving a combination of T-cell dysfunction, a Th2 cell response, and target cell (macrophage) hyporesponsiveness.