role of macrophages in early host resistance to respiratory acinetobacter baumannii infection巨噬细胞在宿主抵抗早期呼吸鲍曼不动杆菌感染.pdfVIP

Role of Macrophages in Early Host Resistance to Respiratory Acinetobacter baumannii Infection 1 ¤ 1 1 2 1 Hongyu Qiu * , Rhonda KuoLee , Greg Harris , Nico Van Rooijen , Girishchandra B. Patel , Wangxue Chen1,3* 1 Institute for Biological Sciences, National Research Council Canada, Ottawa, Ontario, Canada, 2 Department of Molecular Cell Biology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands, 3 Department of Biology, Brock University, St. Catharines, Ontario, Canada Abstract Acinetobacter baumannii is an emerging bacterial pathogen that causes nosocomial pneumonia and other infections. Although it is recognized as an increasing threat to immunocompromised patients, the mechanism of host defense against A. baumannii infection remains poorly understood. In this study, we examined the potential role of macrophages in host defense against A. baumannii infection using in vitro macrophage culture and the mouse model of intranasal (i.n.) infection. Large numbers of A. baumannii were taken up by alveolar macrophages in vivo as early as 4 h after i.n. inoculation. By 24 h, the infection induced significant recruitment and activation (enhanced expression of CD80, CD86 and MHC-II) of macrophages into bronchoalveolar spaces. In vitro cell culture studies showed that A. baumannii were phagocytosed by J774A.1 (J774) macrophage-like cells within 10 minutes of co-incubation, and this uptake was microfilament- and microtubule-dependent. Moreover, the viability of phagocytosed bacteria dropped significantly between 24 and 48 h after co-incubation. Infection of J774 cells by A. baumannii resulted in the production of large amounts of proinfl