沙眼衣原体小鼠肺炎菌株呼吸道感染诱导肺泡巨噬细胞和肺间质巨噬细胞浸润并极化

Chlamydia muridarum respiratory infection induces infiltration and polarization of alveolar macrophages and pulmonary interstitial macrophages

目的探讨沙眼衣原体呼吸道感染对肺泡巨噬细胞(alveolar macrophages,AMs)和肺间质巨噬细胞(interstitial macrophages,IMs)浸润并向M1型或M2型极化的影响。方法C57BL/6小鼠以鼻腔吸入沙眼衣原体小鼠肺炎菌株(Chlamydia muridarum,Cm)建立小鼠沙眼衣原体呼吸道感染模型。采用流式细胞术检测Cm呼吸道感染后0 d、3 d、7 d、14 d肺组织中AMs(CD45^(+)F4/80^(+)CD11c^(+))和IMs(CD45^(+)F4/80^(+)CD11c-)比例并分析细胞数目,同时检测AMs和IMs中M1型巨噬细胞(CD80^(+)、CD86^(+)、MHCⅡ^(+)、iNOS^(+)细胞)比例和M2型巨噬细胞(CD206^(+)、Arg1^(+)细胞)比例。结果(1)Cm呼吸道感染诱导AMs和IMs浸润,与未感染组(0 d)比较,感染后3 d AMs和IMs比例和数目显著增加(P<0.05和P<0.01),感染后7 d AMs和IMs数目均达峰值(P<0.001)。(2)与未感染组比较,感染后3 d AMs中CD80^(+)和CD86^(+)细胞比例明显升高(P<0.05和P<0.01);AMs中MHCⅡ^(+)细胞比例在感染后持续升高,于14 d达峰值(P<0.05),CD206^(+)细胞比例在感染后持续降低(P<0.05)。(3)与未感染组比较,感染后3 d IMs中CD80^(+)和CD86^(+)细胞比例显著升高(P<0.05和P<0.001),感染后14 d MHCⅡ^(+)细胞比例明显升高(P<0.01),CD206^(+)细胞比例变化差异无统计学意义。(4)AMs中iNOS^(+)细胞比例在感染后持续升高(P<0.01);AMs中Arg1^(+)细胞比例在感染后持续降低,与未感染组比较,感染后7 d和14 d显著降低(P<0.05)。IMs中iNOS^(+)细胞比例于感染后7 d达峰值(P<0.001),IMs中Arg1^(+)细胞比例变化差异无统计学意义。结论Cm呼吸道感染诱导AMs和IMs浸润并刺激AMs和IMs向M1型巨噬细胞极化,减弱AMs中M2型巨噬细胞极化水平,而对IMs中M2型巨噬细胞极化无显著影响。

Objective To investigate the effects of Chlamydia muridarum(Cm)respiratory tract infection on the infiltration and polarization of alveolar macrophages(AMs)and pulmonary interstitial macrophages(IMs).Methods A C57BL/6 mouse model of Cm respiratory tract infection was established through nasal inhalation.Flow cytometry was used to detect AMs(CD45^(+)F4/80^(+)CD11c^(+))and IMs(CD45^(+)F4/80^(+)CD11c-)in lung tissues at 0,3,7 and 14 d after Cm respiratory tract infection.The proportions of M1(CD80^(+),CD86^(+),MHCⅡ^(+),iNOS^(+))and M2(CD206^(+),Arg1^(+))macrophages in AMs and IMs were also detected.Results(1)Cm respiratory tract infection induced the infiltration of AMs and IMs.Compared with the uninfected group(0 d),the proportions and the numbers of AMs and IMs of were significantly increased 3 d after infection(P<0.05,P<0.01).The numbers of AMs and IMs reached the peak 7 d after infection(P<0.001).(2)Compared with the uninfected group,the proportions of CD80^(+)and CD86^(+)cells in AMs were significantly up-regulated 3 d after infection(P<0.05,P<0.01);the proportion of MHCⅡ^(+)cells in AMs increased after infection and reached the peak at 14 d(P<0.05),while the proportion of CD206^(+)cells decreased after infection(P<0.05).(3)Compared with the uninfected group,the proportions of CD80^(+)and CD86^(+)cells in IMs were increased 3 d after infection(P<0.05,P<0.001)and the proportion of MHCⅡ^(+)cells was significantly increased 14 d after infection(P<0.01),while there was no significant change in the proportion of CD206^(+)cells.(4)In AMs,the proportion of iNOS^(+)cells increased continuously after infection(P<0.01),while the proportion of Arg1^(+)cells decreased continuously after infection,especially at 7 d and 14 d(P<0.05).In IMs,the proportion of iNOS^(+)cells reached the peak at 7 d(P<0.001),but the proportion of Arg1^(+)cells showed no significant change after infection.Conclusions Cm respiratory tract infection induced the infiltration of AMs and IMs,stimulated the polarization of AMs and IMs towards the M1 phenotype and weakened the polarization of AMs to M2 macrophages,but had no significant influence on the polarization of IMs towards the M2 phenotype.