Immunology Program, Department of Pathology, University of Michigan Medical School, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Immunol Invest. 2011;40(7-8):692-722. doi: 10.3109/08820139.2011.578270. Epub 2011 May 19.
Triggering receptor expressed on myeloid cells-1 (TREM-1) expression is increased during pulmonary fungal infection suggesting that this receptor might be involved in anti-fungal immune responses. To address the role of TREM-1 in a murine model of fungal allergic airway disease, A. fumigatus-sensitized CBA/J mice received by intratracheal injection a mixture of live A. fumigatus conidia and one of a control adenovirus vector (Ad70), an adenovirus containing a gene encoding for the extracellular domain of mouse TREM-1 and the F(c) portion of human IgG (AdTREM-1Ig; a soluble inhibitor of TREM-1 function), or an adenovirus containing mouse DAP12 (AdDAP12; DAP12 is an intracellular adaptor protein required for TREM-1 signaling), and examined at various days after challenge. Whole lung TREM-1 levels peaked at day 3 whereas circulating TREM-1 levels peaked at day 30 in this fungal asthma model. AdTREM-1Ig-treated mice exhibited significantly higher airway hyperresponsiveness following methacholine challenge compared with Ad70- and AdDAP12-treated mice. Whole lung analysis of AdTREM-1Ig treated mice revealed markedly higher amounts of fungal material compared with the other groups. ELISA analysis of whole lung and bronchoalveolar lavage samples indicated that several pro-allergic cytokine and chemokines including CCL17 and CCL22 were significantly increased in the AdTREM-1Ig group compared with the other groups. Finally, Pam3Cys and soluble Aspergillus antigens induced TREM-1 transcript expression in macrophages in a TLR2 dependent manner. In conclusion, TREM-1 modulates the immune response directed against A. fumigatus during experimental fungal asthma.
髓系细胞触发受体-1（TREM-1）在肺部真菌感染期间的表达增加，表明该受体可能参与抗真菌免疫反应。为了研究 TREM-1 在真菌性变应性气道疾病的小鼠模型中的作用，用经气管内注射活烟曲霉菌分生孢子和对照腺病毒载体（Ad70）、一种含有编码小鼠 TREM-1 胞外结构域和人 IgG F(c)部分的基因的腺病毒（AdTREM-1Ig；一种 TREM-1 功能的可溶性抑制剂）或一种含有小鼠 DAP12 的腺病毒（AdDAP12；DAP12 是 TREM-1 信号传导所必需的细胞内衔接蛋白）的混合物对 A. fumigatus 致敏的 CBA/J 小鼠进行处理，并在攻毒后不同时间进行检查。在该真菌性哮喘模型中，整个肺 TREM-1 水平在第 3 天达到峰值，而循环 TREM-1 水平在第 30 天达到峰值。与 Ad70 和 AdDAP12 处理的小鼠相比，AdTREM-1Ig 处理的小鼠在乙酰甲胆碱挑战后表现出明显更高的气道高反应性。与其他组相比，AdTREM-1Ig 处理的小鼠的整个肺分析显示出明显更高量的真菌材料。整个肺和支气管肺泡灌洗液样品的 ELISA 分析表明，与其他组相比，AdTREM-1Ig 组中几种促变应性细胞因子和趋化因子（包括 CCL17 和 CCL22）显著增加。最后，Pam3Cys 和可溶性曲霉菌抗原以 TLR2 依赖的方式诱导巨噬细胞中 TREM-1 转录物的表达。总之，TREM-1 在实验性真菌性哮喘期间调节针对 A. fumigatus 的免疫反应。
