Macrophages and Galectin 3 Control Bacterial Burden in Acute and Subacute Murine Leptospirosis That Determines Chronic Kidney Fibrosis.
Macrophages and Galectin 3 Control Bacterial Burden in Acute and Subacute Murine Leptospirosis That Determines Chronic Kidney Fibrosis.
复制标题
DOI：
10.3389/fcimb.2018.00384
复制
发表时间：
2018
影响因子：
5.7
通讯作者：
Gómez RM
中科院分区：
文献类型：
--
作者：
Ferrer MF;Scharrig E;Charo N;Rípodas AL;Drut R;Carrera Silva EA;Nagel A;Nally JE;Montes de Oca DP;Schattner M;Gómez RM
以前的研究表明，巨噬细胞可能有助于急性钩端螺旋体传播，以及在肾纤维化中发挥重要作用。我们的目的是表征巨噬细胞和半乳糖凝集素3（Gal-3）的生存，临床过程中，细菌负荷，间质性肾炎，慢性肾纤维化钩端螺旋体（LIC）诱导的实验性小鼠钩端螺旋体病的作用。通过脂质体包封的氯膦酸盐治疗耗尽巨噬细胞并感染LIC的C57 BL/6 J小鼠相对于未治疗的感染小鼠呈现更高的细菌负荷，具有减少的亚急性肾炎和增强的慢性肾纤维化。此外，与C57 BL/6 J野生型小鼠相比，Gal-3被破坏的小鼠（Lgals 3 −/-）中的LIC感染具有更高的细菌负荷，并增强了亚急性肾炎和慢性肾纤维化。慢性纤维化与肾脏中TGF-β1或IL-13的较高转录水平无关。在慢性感染大鼠和野生感染大鼠中发现肾纤维化。另一方面，人成纤维细胞培养物在用LIC处理后表现出向肌成纤维细胞的分化增强。我们的研究结果表明，巨噬细胞和Gal-3在控制LIC负担中起关键作用，但在随后的纤维化中起次要作用。相反，肾纤维化与细菌负荷相关性更好。总之，我们的研究结果不支持巨噬细胞在急性感染和慢性肾纤维化中传播钩端螺旋体的作用。
Previous studies have suggested that macrophages may contribute to acute Leptospira dissemination, as well as having a major role in kidney fibrosis. Our aim was to characterize the role of macrophages and galectin 3 (Gal-3) on the survival, clinical course, bacterial burden, interstitial nephritis, and chronic kidney fibrosis in Leptospira interrogans serovar Copenhageni (LIC)-induced experimental murine leptospirosis. C57BL/6J mice depleted of macrophages by liposome-encapsulated clodronate treatment and infected with LIC presented a higher bacterial burden, had reduced subacute nephritis and enhanced chronic kidney fibrosis relative to untreated, infected mice. Moreover, LIC infection in mice whose Gal-3 was disrupted (Lgals3−/–) had a higher bacterial burden and enhanced subacute nephritis and chronic kidney fibrosis when compared to C57BL/6J wild-type mice. Chronic fibrosis did not correlate with higher transcription levels of TGF-β1 or IL-13 in the kidneys. Kidney fibrosis was found in chronically infected rats as well as in wild infected rats. On the other hand, human fibroblast cultures exhibited enhanced differentiation to myofibroblasts after treatment with LIC. Our results demonstrate that macrophages and Gal-3 play a critical role in controlling the LIC burden but has a minor role in subsequent fibrosis. Instead, kidney fibrosis was better correlated with bacterial burden. Taken together, our results do not support a role for macrophages to disseminate leptospires during acute infection, nor in chronic kidney fibrosis.