title: Role of macrophages in early host resistance to respiratory Acinetobacter baumannii infection.
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 proinflammatory cytokines and chemokines, and moderate amounts of nitric oxide (NO). Prior treatment of J774 cells with NO inhibitors significantly suppressed their bactericidal efficacy (P<0.05). Most importantly, in vivo depletion of alveolar macrophages significantly enhanced the susceptibility of mice to i.n. A. baumannii challenge (P<0.01). These results indicate that macrophages may play an important role in early host defense against A. baumannii infection through the efficient phagocytosis and killing of A. baumannii to limit initial pathogen replication and the secretion of proinflammatory cytokines and chemokines for the rapid recruitment of other innate immune cells such as neutrophils.
authors: Institute for Biological Sciences, National Research Council Canada, Ottawa, Ontario, Canada. HQiu@Cangene.com
authors: Hongyu
authors: H
authors: Qiu
authors: Rhonda
authors: R
authors: KuoLee
authors: Greg
authors: G
authors: Harris
authors: Nico
authors: N
authors: Van Rooijen
authors: Girishchandra B
authors: GB
authors: Patel
authors: Wangxue
authors: W
authors: Chen
mesh_terms: D000151:Acinetobacter Infections / Q000276:immunology* / Q000382:microbiology*; D040981:Acinetobacter baumannii / Q000187:drug effects / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D039521:CD11c Antigen / Q000378:metabolism; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D060467:Disease Resistance / Q000187:drug effects / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D050296:Microbial Viability / Q000187:drug effects; D018448:Models, Immunological; D009569:Nitric Oxide / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000382:microbiology; D013997:Time Factors; D014226:Triazenes / Q000494:pharmacology
chemical_list: C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; D039521:CD11c Antigen; D018925:Chemokines; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D014226:Triazenes; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II