Acinetobacter baumannii has emerged as a major cause of both community-associated and nosocomial pneumonia, but little is known about the cellular and molecular mechanisms of host defense against respiratory infection with this bacterial pathogen. In this study, we examined the role of neutrophils in host resistance to pulmonary A. baumannii infection in a mouse model of intranasal (i.n.) infection. We found that neutrophils were rapidly recruited to the lungs following i.n. inoculation of the pathogen and declined to baseline level upon clearance of the infection. Depletion of neutrophils using monoclonal antibody RB6-8C5 prior to infection resulted in an acute lethal infection that was associated with enhanced bacterial burdens in the lung (P < 0.05) and extrapulmonary dissemination to the spleen. The increased susceptibility to A. baumannii in neutropenic mice was associated with a delay in the mRNA expression and production of early proinflammatory cytokines such as tumor necrosis factor alpha, interleukin-6, keratinocyte chemoattractant protein, monocyte chemoattractant protein 1, and macrophage inflammatory protein 2 (MIP-2) in the lungs and development of severe bronchopneumonia and lymphoid tissue destruction in the spleen. Moreover, i.n. administration of the neutrophil-inducing chemokine MIP-2 to normal mice induced a pulmonary influx of neutrophils and significantly enhanced the clearance of A. baumannii from the lungs (P < 0.01). These results imply that neutrophils play a critical role in host resistance to respiratory A. baumannii infection.

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Although it is recognized that identification and commitment are closely related aspects of employees' psychological attachment to the organization, there has been no analysis of the overlap between multiple dimensions of each construct. In this study, three-component models of organizational identification and commitment were investigated as predictors of turnover intentions and psychological well-being (self-esteem, satisfaction with life, and self-efficacy) among employees (N = 60) of a small organization. Highly identified employees tended to be committed ones, but different dimensions of each construct were specifically linked to various criteria. Affective components of both identification and commitment were negatively associated with turnover intentions, and positive in-group affect (i.e., feelings derived from being a member of the organization) predicted perceptions of self-efficacy. Continuance commitment was distinct from the other predictors, and was negatively related to self-esteem and self-efficacy. The results warrant further efforts to integrate the perspectives of social identity theory and organizational psychology.

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.

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Acinetobacter baumannii is an emerging bacterial pathogen that rapidly develops multiple-drug resistance and is responsible for many nosocomial pulmonary infections. This study investigated the role of the NADPH phagocyte oxidase (phox) and inducible nitric oxide synthase (NOS2) in the host defense against respiratory infection with A. baumannii in mouse models of intranasal A. baumannii infection. gp91 phox؊/؊ mice showed higher susceptibility to A. baumannii infection than wild-type (WT) C57BL/6 mice, with significantly greater bacterial counts in their lungs (1,000-fold) (P < 0.005) and spleens (10-fold) (P < 0.05). Moreover, all of the gp91 phox؊/؊ mice succumbed to infection within 48 h. In contrast, only a moderate increase in bacterial burdens was detected in the lungs of NOS2 ؊/؊ mice, and all NOS2 ؊/؊ mice survived infection. Compared to WT mice, the pulmonary influx of inflammatory cells and serum and local inflammatory cytokine/chemokine responses were not obviously impaired at 4 h and were significantly higher at 24 h (P < 0.05) in gp91 phox؊/؊ mice, but NADPH-deficient neutrophils were unable to control bacterial replication and extrapulmonary dissemination. Thus, NADPH phagocyte oxidase appears to play a crucial role in the neutrophil-mediated host defense against A. baumannii.

Acinetobacter baumannii is an important nosocomial pathogen. Mechanisms that allow A. baumannii to cause human infection are still poorly understood. Iron is an essential nutrient for bacterial growth in vivo, and the multiplicity of iron uptake systems in A. baumannii suggests that iron acquisition contributes to the ability of A. baumannii to cause infection. In Gram-negative bacteria, active transport of ferrisiderophores and heme relies on the conserved TonB-ExbB-ExbD energytransducing complex, while active uptake of ferrous iron is mediated by the Feo system. The A. baumannii genome invariably contains three tonB genes (tonB1, tonB2, and tonB3), whose role in iron uptake is poorly understood. Here, we generated A. baumannii mutants with knockout mutations in the feo and/or tonB gene. We report that tonB3 is essential for A. baumannii growth under iron-limiting conditions, whereas tonB1, tonB2, and feoB appear to be dispensable for ferric iron uptake. tonB3 deletion resulted in reduced intracellular iron content despite siderophore overproduction, supporting a key role of TonB3 in iron uptake. In contrast to the case for tonB1 and tonB2, the promoters of tonB3 and feo contain functional Fur boxes and are upregulated in iron-poor media. Both TonB3 and Feo systems are required for growth in complement-free human serum and contribute to resistance to the bactericidal activity of normal human serum, but only TonB3 appears to be essential for virulence in insect and mouse models of infection. Our findings highlight a central role of the TonB3 system for A. baumannii pathogenicity. Hence, TonB3 represents a promising target for novel antibacterial therapies and for the generation of attenuated vaccine strains.

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