Infection with L. donovani affects mainly visceral organs. Importantly, the parasitic load differs in different visceral organs; therefore there is a need to understand the organ specific immune regulation, particularly in the spleen and liver. Comparative studies between these organs in Leishmania infected hamster (Mesocricetus auratus) are lacking. Our study highlights the importance of eicosanoids in the organ specific pathology of visceral leishmaniasis. Among other immune cells, macrophages (mφ) which harbor Leishmania parasite are major producers of eicosanoids. In this study, we intend to explore linkage between organ specific immune response and eicosanoids. We suggest that eicosanoids (early immune modulators) and their organ specific expressions, possibly tune the outcome of mφ differently at different sites. We have observed that liver showed better containment of parasitic load than spleen, where we have found higher expression of 5-lipoxygenase (5-LO) enzyme along with IL-12 and iNOS. However, in spleen, enzymes of the PGE2 pathway i.e. PGE2 synthases (cytosolic and microsomal) along with IL-10 were predominantly higher. To further corroborate our findings, in vitro assays were carried out using purified eicosanoids (LTB4 and PGE2) and the inhibitors of these pathways. Findings establish that the 5-lipoxygenase pathway (i.e. LTB4) is anti-parasitic and its inhibition increases the parasitic load (qPCR based kDNA detection). On the contrary, PGES pathway (i.e. PGE2) supports establishment of infection in mφ. Taken together, 5-LO pathway plays a protective role in liver during L. donovani infection. However, the PGES pathway favors the parasite growth, particularly in the spleen at a later stage.

中文翻译：

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通过5-脂氧合酶和PGE2合成酶在内脏利什曼病中的差异表达确定寄生虫负荷。

多诺氏乳杆菌的感染主要影响内脏器官。重要的是，不同内脏器官的寄生负荷不同。因此，有必要了解器官特异性免疫调节，特别是在脾脏和肝脏中。在利什曼原虫感染的仓鼠（Mesocricetus auratus）中这些器官之间缺乏比较研究。我们的研究突出了类花生酸在内脏利什曼病的特定器官病理学中的重要性。在其他免疫细胞中，带有利什曼原虫寄生虫的巨噬细胞（mφ）是类花生酸的主要生产者。在这项研究中，我们打算探索器官特异性免疫反应和类花生酸之间的联系。我们建议类二十烷酸（早期免疫调节剂）及其器官特异性表达，可能在不同部位对mφ的结果进行不同的调节。我们已经观察到肝脏显示出比脾脏更好的寄生虫负载，在肝脏中我们发现5-脂氧合酶（5-LO）酶以及IL-12和iNOS的表达更高。但是，在脾脏中，PGE2途径的酶（即PGE2合成酶（胞质和微粒体）以及IL-10）主要较高。为了进一步证实我们的发现，使用纯化的类花生酸（LTB4和PGE2）和这些途径的抑制剂进行了体外测定。结果表明5-脂氧合酶途径（即LTB4）具有抗寄生虫性，其抑制作用会增加寄生虫负荷（基于qPCR的kDNA检测）。相反，PGES途径（即PGE2）支持在mφ中建立感染。两者合计，5-LO途径在L. donovani感染期间对肝脏起保护作用。然而，