期刊
JOURNAL OF IMMUNOLOGY
卷 202, 期 5, 页码 1453-1464出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1801249
关键词
-
类别
资金
- Deutsche Forschungsgemeinschaft [CRC1181, GRK1660]
- Bundesministerium fur Bildung und Forschung [Infect-ERA IV [031L0126]]
- Interdisciplinary Center for Clinical Research of the University Hospital Erlangen
Arginase (Arg) 1 is expressed by hematopoietic (e.g., macrophages) and nonhematopoietic cells (e.g., endothelial cells) and converts L-arginine into ornithine and urea. The enzyme is implicated in tissue repair but also antagonizes the production of NO by type 2 NO synthase in myeloid cells and thereby impedes the control of intracellular parasites such as Leishmania major. In this study, we tested whether Arg1 is required for spontaneous healing of acute cutaneous leishmaniasis in C57BL/6 mice and for lifelong parasite persistence in draining lymph nodes (dLNs) of healed mice. In vitro, bone marrow-derived macrophages and lymphoid endothelial cells readily expressed Arg1 in response to IL-4 and/or IL-13, whereas skin or dLN fibroblasts failed to do so, even during hypoxia. In vivo, Arg1 was found in skin lesions and, to a much lower extent, also in dLNs of acutely infected C57BL/6 mice but became undetectable at both sites after healing. Deletion of Arg1 in hematopoietic and endothelial cells using Tie2Cre(+/-) Arg1(fl/fl) C57BL/6 mice abolished the expression of Arg1 in skin lesions and dLNs but did not affect development and resolution of skin lesions, parasite burden, NO production, or host cell tropism of L. major during the acute or persistent phase of infection. Similar to wild-type controls, parasites persisting in Arg1-deficient mice favored NO synthase 2-negative areas and mainly resided in myeloid cells and fibroblasts. We conclude that Arg1 expression by hematopoietic and endothelial cells is completely dispensable for clinical resolution of cutaneous leishmaniasis and for long-term persistence of L. major.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据