Inhibitor of serine peptidase 2 enhances Leishmania major survival in the skin through control of monocytes and monocyte-derived cells.
Inhibitor of serine peptidase 2 enhances Leishmania major survival in the skin through control of monocytes and monocyte-derived cells.
复制标题
DOI：
10.1096/fj.201700797r
复制
发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Myburgh E
中科院分区：
文献类型：
--
作者：
Goundry A;Romano A;Lima APCA;Mottram JC;Myburgh E
大利什曼原虫是一种被忽视的热带疾病--皮肤利什曼病的病原体。在小鼠中，对利什曼原虫的保护性免疫与炎症反应有关。在这里，我们使用非侵入性成像和转基因L.main，评估了耳部长期、低剂量皮内感染期间病变部位炎症反应的动态。中性粒细胞和单核细胞在1-4d和2-4wk出现明显的浸润，而真皮巨噬细胞和树突状细胞(DC)的数量在最初的几天才略有增加。髓过氧化物酶活性的定量全身生物发光成像和寄生虫载量的定量表明，利什曼原虫毒力因子是丝氨酸肽酶2(ISP2)的抑制剂，需要调节吞噬细胞的激活，并且对寄生虫在感染部位的生存至关重要。ISP2对单核细胞、单核细胞来源的巨噬细胞和单核细胞来源的DC(MODC)的内流起控制作用，并需要减少单核细胞、单核细胞来源的细胞和真皮DC中iNOS的表达，减少MODC中CD80的表达和原位干扰素-γ的水平。我们的发现表明，在急性感染期间，主要利什曼原虫在真皮中存活率的增加与通过ISP2下调炎性单核细胞和单核细胞衍生细胞有关。-Goundry，A.，Romano，A.，Lima，A.P.C.A.，Mottram，J.C.，Myburgh，E.丝氨酸肽酶2的抑制剂通过控制单核细胞和单核细胞衍生细胞，提高了利什曼原虫在皮肤中的主要存活率。
Leishmania major is the causative agent of the neglected tropical disease, cutaneous leishmaniasis. In the mouse, protective immunity to Leishmania is associated with inflammatory responses. Here, we assess the dynamics of the inflammatory responses at the lesion site during experimental long-term, low-dose intradermal infection of the ear, employing noninvasive imaging and genetically modified L. major. Significant infiltrates of neutrophils and monocytes occurred at 1–4 d and 2–4 wk, whereas dermal macrophage and dendritic cell (DC) numbers were only slightly elevated in the first days. Quantitative whole-body bioluminescence imaging of myeloperoxidase activity and the quantification of parasite loads indicated that the Leishmania virulence factor, inhibitor of serine peptidase 2 (ISP2), is required to modulate phagocyte activation and is important for parasite survival at the infection site. ISP2 played a role in the control of monocyte, monocyte-derived macrophage, and monocyte-derived DC (moDC) influx, and was required to reduce iNOS expression in monocytes, monocyte-derived cells, and dermal DCs; the expression of CD80 in moDCs; and levels of IFN-γ in situ. Our findings indicate that the increased survival of L. major in the dermis during acute infection is associated with the down-regulation of inflammatory monocytes and monocyte-derived cells via ISP2.—Goundry, A., Romano, A., Lima, A. P. C. A., Mottram, J. C., Myburgh, E. Inhibitor of serine peptidase 2 enhances Leishmania major survival in the skin through control of monocytes and monocyte-derived cells.