Dey R, Majumder N, Bhattacharyya Majumdar S, Bhattacharjee S, Banerjee S, Roy S, Majumdar S
Department of Microbiology, Bose Institute, Kolkata, India.
Scand J Immunol. 2007 Dec;66(6):671-83. doi: 10.1111/j.1365-3083.2007.02025.x.
The resolution from leishmanial infection is dependent on the coordinated interactions between the components of the cell mediated immune system and the activation of T-cell population into appropriate cytokine production and the activation of macrophages. Earlier reports established that C-C chemokines particularly macrophage inflammatory protein (MIP)-1alpha and macrophage chemoattractant protein (MCP)-1 restrict the parasitic burden via the regulation of impaired protein kinase C (PKC) signalling and induction of free-radical generation in murine leishmaniasis. This study explored the role of MIP-1alpha and MCP-1 in the induction of T helper 1 (Th1) immune response and suppression of T helper 2 (Th2) response in Leishmania donovani-infected BALB/c mice. These chemokines induced the known pro-inflammatory cytokine interleukin (IL)-12 secretion and inhibited the secretion of anti-inflammatory cytokines IL-10 and transforming growth factor-beta in infected macrophages. Impaired antigen presentation capability of infected macrophages was also restored by the chemokine treatment. C-C chemokine treatment resulted in reduced levels of mRNA expression of IL-10, but increased levels of mRNA expression of IL-12p40, interferon (IFN)-gamma, tumour necrosis factor-alpha and inducible nitric oxide synthase in both liver mononuclear cells as well as in splenocytes, reflecting a switch of CD4+ differentiation from Th2 to Th1. Flow cytometric analysis of infected spleen cells suggested that C-C chemokine treatment enhances the CD4+ T cells to produce increased levels of IFN-gamma. These studies hypothesize a promising immuno-prophylactic effect of chemokines against leishmaniasis by induction of Th1 cytokine release imparting a long-term resistance.
利什曼原虫感染的消退取决于细胞介导免疫系统各组成部分之间的协同相互作用，以及T细胞群体激活以产生适当的细胞因子和巨噬细胞的激活。早期报告表明，C-C趋化因子，特别是巨噬细胞炎性蛋白（MIP）-1α和巨噬细胞趋化蛋白（MCP）-1，通过调节受损的蛋白激酶C（PKC）信号传导和诱导小鼠利什曼病中的自由基生成来限制寄生虫负荷。本研究探讨了MIP-1α和MCP-1在杜氏利什曼原虫感染的BALB/c小鼠中诱导辅助性T细胞1（Th1）免疫反应和抑制辅助性T细胞2（Th2）反应中的作用。这些趋化因子诱导了已知的促炎细胞因子白细胞介素（IL）-12的分泌，并抑制了感染巨噬细胞中抗炎细胞因子IL-10和转化生长因子-β的分泌。趋化因子处理还恢复了感染巨噬细胞受损的抗原呈递能力。C-C趋化因子处理导致肝脏单核细胞和脾细胞中IL-10的mRNA表达水平降低，但IL-12p40、干扰素（IFN）-γ、肿瘤坏死因子-α和诱导型一氧化氮合酶的mRNA表达水平升高，反映了CD4+分化从Th2向Th1的转变。对感染脾细胞的流式细胞术分析表明，C-C趋化因子处理增强了CD4+T细胞产生更高水平的IFN-γ。这些研究推测趋化因子通过诱导Th1细胞因子释放赋予长期抗性，对利什曼病具有有前景的免疫预防作用。
