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墨西哥利什曼原虫在感染早期诱导有限的单核细胞和单核细胞衍生的树突状细胞的募集和激活。

Leishmania mexicana induces limited recruitment and activation of monocytes and monocyte-derived dendritic cells early during infection.

机构信息

Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.

出版信息

PLoS Negl Trop Dis. 2012;6(10):e1858. doi: 10.1371/journal.pntd.0001858. Epub 2012 Oct 18.

Abstract

While C57BL/6 mice infected in the ear with L. major mount a vigorous Th1 response and resolve their lesions, the Th1 response in C57BL/6 mice infected with L. mexicana is more limited, resulting in chronic, non-healing lesions. The aim of this study was to determine if the limited immune response following infection with L. mexicana is related to a deficiency in the ability of monocyte-derived dendritic cells (mo-DCs) to prime a sufficient Th1 response. To address this issue we compared the early immune response following L. mexicana infection with that seen in L. major infected mice. Our data show that fewer monocytes are recruited to the lesions of L. mexicana infected mice as compared to mice infected with L. major. Moreover, monocytes that differentiate into mo-DCs in L. mexicana lesions produced less iNOS and migrated less efficiently to the draining lymph node as compared to those from L. major infected mice. Treatment of L. mexicana infected mice with α-IL-10R antibody resulted in increased recruitment of monocytes to the lesion along with greater production of IFN-γ and iNOS. Additionally, injection of DCs into the ear at the time of infection with L. mexicana also led to a more robust Th1 response. Taken together, these data suggest that during L. mexicana infection reduced recruitment, activation and subsequent migration of monocytes and mo-DCs to the draining lymph nodes may result in the insufficient priming of a Th1 response.

摘要

当 C57BL/6 小鼠感染 L. major 后,其耳部会引发强烈的 Th1 反应并清除病变,但 C57BL/6 小鼠感染 L. mexicana 后,Th1 反应更为有限,导致慢性、不愈的病变。本研究旨在确定感染 L. mexicana 后,有限的免疫反应是否与单核细胞衍生的树突状细胞(mo-DCs)产生足够 Th1 反应的能力缺陷有关。为了解决这个问题,我们比较了 L. mexicana 感染后的早期免疫反应与 L. major 感染小鼠的反应。我们的数据表明,与感染 L. major 的小鼠相比,感染 L. mexicana 的小鼠病变中募集的单核细胞更少。此外,与感染 L. major 的小鼠相比,在 L. mexicana 病变中分化为 mo-DCs 的单核细胞产生的 iNOS 更少,迁移到引流淋巴结的效率也更低。用α-IL-10R 抗体治疗 L. mexicana 感染的小鼠可增加单核细胞向病变部位的募集,同时增加 IFN-γ 和 iNOS 的产生。此外,在感染 L. mexicana 时向耳部注射 DC 也可导致更强烈的 Th1 反应。总之,这些数据表明,在 L. mexicana 感染期间,单核细胞和 mo-DCs 向引流淋巴结的募集、激活和随后的迁移减少,可能导致 Th1 反应的不足。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6a8/3475671/0a89b4ac9fc9/pntd.0001858.g001.jpg

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