IL-33敲除促进弓形虫感染小鼠腹腔巨噬细胞的M1偏移

IL-33 deficiency promotes M1 polarization of mouse peritoneal macrophages infected with Toxoplasma gondii

目的研究IL-33敲除(IL-33^(-/-))对小鼠急性弓形虫感染腹腔巨噬细胞(pMφ)极化的影响,探讨IL-33^(-/-)在弓形虫感染免疫应答中的作用。方法收集C57BL/6IL-33^(-/-)小鼠和野生型(WT)小鼠pMφ,各分为弓形虫感染组和未感染组,比较各组pMφ感染率、细胞因子及表面分子表达水平的变化。结果 IL-33^(-/-)小鼠pMφ弓形虫感染30 min后的感染率低于WT小鼠(t=-2.49,P<0.05);IL-33^(-/-)小鼠感染组pMφM1型标志物NO(t=29.71,P<0.05)、MHCⅡ(t=19.05,P<0.05)、TLR4(t=8.34,P<0.05)表达高于WT小鼠感染组,而M2型标志物CD206表达低于WT小鼠感染组(t=-3.34,P<0.05);感染组小鼠pMφNO、IL-10、TNF-α、MHCⅡ类分子及CD86的表达高于各自未感染对照组;IL-33敲除和弓形虫感染对IL-33^(-/-)与WT小鼠pMφMHCⅡ(F=5.25,P<0.05)、TLR2(F=14.88,P<0.05)分子的表达有交互作用。结论在急性弓形虫感染早期,IL-33敲除驱动小鼠pMφ向M1方向极化,促进pMφ抗感染。

We investigated the effect of IL-33 knockout on the polarization of peritoneal macrophages from mouse with acute Toxoplasma infection, in order to uncover the function of IL-33 knockout in mice macrophages with acute Toxoplasma infection. pMφ was isolated from C57BL/6 wild type and IL-33 deficient mice and divided into Toxoplasma infected group and control group respectively. Infection rate of pMφ was determined; the mRNA of iNOS, Arg-1, IL-1, IL-10 and IL-12 were analyzed by real-time PCR; the secretion of IL-12, TNF-α, IL-10 and NO were detected by ELISA and Griess method respectively; the surface molecules （CD80, CD86, CD206, TLR4, TLR2, MHCⅡ） were analyzed by flow cytometry. Results showed that the infection rate of pMφ was deceased in IL-33^-/- mice compared with wild-type mice （t=-2.49,P〈0.05）; the expression of M1 makers NO（t=29.71,P〈0.05）, MHCⅡ（t=19.05,P〈0.05）, CD86 and TLR4（t=8.34,P〈0.05） were increased （P〈0.01） while the M2 maker （CD206） was down-regulated in IL-33^-/- mice infected with Toxoplasma than that in the wild-type infected group; the secretion of NO, IL-10, TNF-α and the expression of MHCⅡand CD86 were higher in infected group of both IL-33^-/- and wild-type mice compared with uninfected control group respectively （P〈0.01）. Results suggest that IL-33 knockout promote the secretion of NO and the expression of MHCⅡ（F=14.88,P〈0.05）, CD86 and TLR4 via driving polarization of M1 macrophages, thereby enhancing the immune protection in acute Toxoplasma infection.