马尔尼菲蓝状菌（TM）能在宿主的巨噬细胞内存活并导致侵袭感染，侵袭感染程度取决于病原菌的毒力和宿主的免疫状态。我们前期的研究发现人感染ＴＭ的皮损组织和小鼠感染TM的内脏组织中单核／巨噬细胞以M2型占优势，而且精氨酸酶表达增强。ＴＭ如何影响巨噬细胞的极化机制尚未明确。假设ＴＭ通过调节细胞内L-精氨酸代谢通路诱导巨噬细胞极化。本研究拟通过沉默TM和巨噬细胞精氨酸酶基因，以及使用精氨酸酶抑制剂或L-精氨酸，调控TM和巨噬细胞精氨酸代谢通路。在抑制或增强精氨酸酶活性情况下，评价TM细胞形态学变化、体外TM感染后巨噬细胞精氨酸酶及一氧化氮合酶活性、一氧化氮生成、细胞因子分泌和细胞极化情况，构建小鼠感染TM模型评估精氨酸酶代谢通路对TM致病力的影响以及巨噬细胞体内极化过程。从分子、细胞和动物水平，系统揭示TM调节巨噬细胞L-精氨酸代谢以及驱动巨噬细胞极化的机制，为TM感染的发病机制和治疗提供思路。

Talaromyces marneffei (TM) survive　in the host macrophage and cause invasive infection depending on both pathogen virulence and host immune competence. Our previous research showed that monocyte/macrophage presented as M2 type predominant in skin lesions of human infection and internal organ tissues of mouse infection, as well as increased activity of arginase．However, the mechanism of TM modulate macrophage polarization　remain　unknown．We hypothesis　that　TM　induce　macrophage　polarization　through　regulation metabolic pathway of L-arginine. This research aim to regulate metabolic pathway of L-arginine within TM or macrophage via knock down arginine gene of TM or macrophage， as well as arginase inhibitor is applied or L-arginine is supplemented. Under the condition of arginase inhibition or activation, morphology of TM cells will be assessed, as well as activity of arginase and iNOS, NO production, cytokine secretion and cell polarization of macrophage will be detected after infection by TM. Furthermore, the virulence of TM and the development of macrophage polarization in the host will be assessed by mouse infection model. We are trying to explore the mechanism of TM regulate metabolic pathway of L-arginine and modulate macrophage polarization, and we expect to find clues for pathogenesis of TM infection and therapy in the future.