Objective: To investigate the expression of triggering receptor expressed on myeloid cells receptor-1 (TREM-1) in plasma and bronchoalveolar lavage fluid (BALF) and its correlation with Galactomannan, IFNγ, IL-6 and IL-10 in Aspergillus infected mice. Methods: Cyclophosphamide(CTX) was intraperitoneally injected and fumigatus spore suspension was inhaled by nose to establish the immunocompromised invasive pulmonary aspergillosis(IPA) mouse model.Healthy controls, immunocompromised only and IPA only groups were also established. Each group had 6 mice. After inoculation, mice were sacrificed. Lung tissue specimens, BALF, and plasma samples were collected. Plasma and BALF soluble TREM-1 (sTREM-1), Galactomannan, IFNγ, IL-6, and IL-10 were detected by ELISA. Results: Positive Aspergillus fumigatus was found by tissue culture in the lung. Infiltration of inflammatory cells, blood congestion and interstitial lung tissue injury were observed in histological sections of both IPA and immunocompromised IPA mice. Compared to IPA group [(453.78±74.18) ng/L, P<0.001; (10.21±1.46) ng/L, P<0.001] and control group [(245.16±65.85) ng/L, P<0.001; (6.60±3.74) ng/L, P<0.001], the plasma and BALF sTREM-1 significantly increased in immunocompromised IPA group [(1 537.64±359.52) ng/L; (20.12±2.72) ng/L]. Compared to control group, both the BALF sTREM-1 in IPA group (P=0.041) and the plasma and BALF Galactomannan, IFNγ, IL-6, and IL-10 levels in IPA and immunocompromised IPA groups were significantly higher (P<0.01). Pearson correlation analysis showed that plasma and BALF sTREM-1 were significantly correlated with Galactomannan (r=0.83, P<0.001; r=0.82, P<0.001), IFNγ (r=0.79, P<0.001; r=0.61, P<0.01), IL-6 (r=0.81, P<0.001; r=0.66, P<0.01), and IL-10 (r=0.70, P=0.001; r=0.54, P=0.02). Conclusions: Plasma and BALF sTREM-1 appears highly expressed in Aspergillus infected mice. sTREM-1 in mice plasma and BALF is closely correlated with Galactomannan, IFNγ, IL-6, and IL-10 levels, which suggests that sTREM-1 has great diagnostic value during invasive fungal infection.
目的： 探讨真菌感染小鼠血浆和支气管肺泡灌洗液(BALF)中髓样细胞表达触发受体－1(TREM－1)表达及其意义。 方法： 小鼠分为3组，健康对照组(免疫正常，无曲霉接种)、侵袭性肺曲霉菌病(IPA)组(免疫正常＋曲霉接种)、免疫抑制曲霉菌感染组，每组6只。建立小鼠曲霉感染模型后处死取血、BALF和肺组织。采用ELISA法检测血浆和BALF中可溶性TREM－1、半乳甘露聚糖、IFNγ、IL－6、IL－10水平，肺组织标本进行组织匀浆培养和病理切片染色。 结果： IPA组、免疫抑制曲霉菌感染组小鼠肺组织曲霉培养阳性，病理表现为急性炎性细胞浸润、肺间质充血、肺泡结构破坏，提示建模成功。免疫抑制曲霉菌感染组小鼠血浆和BALF中可溶性TREM－1[(1 537.64±359.52) ng/L；(20.12±2.72) ng/L]显著高于IPA组[(453.78±74.18) ng/L，P<0.001；(10.21±1.46) ng/L，P<0.001]和健康对照组[(245.16±65.85) ng/L，P<0.001；(6.60±3.74) ng/L，P<0.001]，IPA组小鼠BALF中可溶性TREM－1也显著高于健康对照组(P＝0.041)。与健康对照组比，IPA组和免疫抑制曲霉菌感染组小鼠血浆和BALF中半乳甘露聚糖、IFNγ、IL－6、IL－10水平明显增高(P<0.01)。相关性分析显示，小鼠血浆和BALF中可溶性TREM－1分别与血浆和BALF中半乳甘露聚糖(r＝0.83，P<0.001；r＝0.82，P<0.001)、IFNγ(r＝0.79，P<0.001；r＝0.61，P<0.01)、IL－6(r＝0.81，P<0.001；r＝0.66，P<0.01)、IL－10(r＝0.70，P＝0.001；r＝0.54，P＝0.02)呈正相关。 结论： 免疫抑制和非免疫抑制状态下曲霉菌感染小鼠血浆和BALF中可溶性TREM－1水平明显升高，与真菌感染负荷和炎性因子水平密切相关，具有重要的临床诊断价值。.
Keywords: Immunosuppression; Invasive pulmonary aspergillosis; Triggering receptor expressed on myeloid cells receptor-1.