Interleukin 10- and Fcγ receptor-deficient mice resolve Leishmania mexicana lesions
Interleukin 10- and Fcγ receptor-deficient mice resolve Leishmania mexicana lesions
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DOI：
10.1128/iai.73.4.2101-2108.2005
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发表时间：
2005-04-01
影响因子：
3.1
通讯作者：
Scott, P
中科院分区：
文献类型：
--
作者：
Buxbaum, LU;Scott, P
用墨西哥利什曼原虫感染C57 BL/6（136）小鼠与最小免疫应答和慢性疾病相关。在这里，我们表明，B6白细胞介素10（-/-）（IL-10（-/-））小鼠解决他们的病变，并表现出增加γ干扰素（IFN-γ），一氧化氮的生产，和迟发型超敏反应。这种增强的抗性依赖于IL-12 p40，因为L.用抗IL-12 p40单克隆抗体感染IL-10（-/-）小鼠的墨西哥线虫的愈合被废除。抗体调理L.在体外，Mexicana通过B6巨噬细胞诱导IL-10产生，暗示抗体结合Fe受体是这种感染中IL-10产生的机制。此外，B6 FcR γ（-/-）小鼠分辨L. mexicana病变，并且这些小鼠的淋巴结细胞比感染的野生型小鼠产生更少的IL-10和更多的IFN-γ。这些数据表明，去除IL-10或Fc γ R导致L分离。mexicana疾病的研究，并支持了一个模型，其中Fc γ R被L.墨西哥结合的免疫球蛋白G促进IL-10的产生，导致慢性疾病。
Infection of C57BL/6 (136) mice with Leishmania mexicana is associated with a minimal immune response and chronic disease. Here we show that B6 interleukin 10(-/-) (IL-10(-/-)) mice resolve their lesions and exhibit increased gamma interferon (IFN-gamma), nitric oxide production, and delayed-type hypersensitivity. This enhanced resistance was dependent upon IL-12p40, since treatment of L. mexicana-infected IL-10(-/-) mice with anti-1L-12p40 monoclonal antibody abrogated healing. Antibody-opsonized L. mexicana induced IL-10 production by B6 macrophages in vitro, implicating antibody binding to Fe receptors as a mechanism involved in IL-10 production in this infection. Furthermore, B6 FcR gamma(-/-) mice resolve L. mexicana lesions, and lymph node cells from these mice produced less IL-10 and more IFN-gamma than cells from infected wild-type mice. These data demonstrate that removal of IL-10 or Fc gamma R leads to resolution of L. mexicana disease and support a model in which ligation of Fc gamma R by L. mexicana-bound immunoglobulin G promotes IL-10 production, leading to chronic disease.