CARD9基因敲除小鼠骨髓来源树突状细胞对阿萨希毛孢子菌临床株的免疫反应缺陷

The impairment of immune response against Trichosporon asahii clinical isolate in CARD9 knockout murine bone marrow-derived dendritic cell

目的初步探讨CARD9基因敲除小鼠骨髓来源树突状细胞(bone marrowderived dendritic cell,BMDC)对阿萨希毛孢子菌临床株(Trichosporon asahii,T.asahii)的免疫反应缺陷。方法体外培养野生型(wild type,WT)与CARD9基因敲除型(CARD9knockout,CARD9-/-)小鼠BMDC并分别与热灭活的T.asahii进行共培养,比较两者对菌体的黏附吞噬能力、表面共刺激分子的激活、细胞因子的表达以及两种小鼠感染菌株后的生存率。结果共培养24 h后,WT与CARD9-/-小鼠BMDC对T.asahii的黏附吞噬情况比较未见明显差异;经T.asahii刺激的CARD9-/-小鼠BMDC的CD80、CD86激活情况以及白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α表达水平均明显低于WT小鼠BMDC(P<0.05);感染T.asahii的CARD9-/-小鼠的生存率明显低于WT小鼠(P<0.05)。结论 CARD9-/-小鼠BMDC对T.asahii的免疫反应缺陷主要体现在共刺激分子的激活以及促炎细胞因子的表达,但并未影响其对T.asahii的吞噬识别。

Objective To investigate the impairment of immune response against Trichosporon asahii（T.asahii） clinical isolate in CARD9 knockout murine bone marrow-derived dendritic cell（BMDC）. Methods After in vitro co-culture of BMDCs from wild type mice（WT） and CARD9 knockout mice（CARDg-/-） with heat-killed Zasahii, the phagocytotic ability, costimulatory molecules activation and cytokines production of BMDCs between WT and CARD9-/- were compared. Results Compared with the WT BMDC, the phagocytotic ability of CARD9-/- BMDC was not significantly impaired, but its activation of CD80 and CD86 and the production of IL-6 and TNF-α were significantly lower after co-cultured with Zasahii for 24h. After having been infected by T.asahii, the CARD9-/- mice showed remarkable lower survival rate than the WT mice. Conclusion CARD9-/- BMDC exhibited the defects in costimulatory molecules activation and inflammatory cytokines production but not the phagocytotic ability against T.asahii.