Neutrophils Play an Important Role in Host Resistance to Respiratory Infection with Acinetobacter baumannii in Mice

Abstract

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.

Effect of Dietary Oils on Host Resistance to Fungal Infection in Psychologically Stressed Mice

“…15,16) Treatment of mice with anti-IFN-monoclonal antibody resulted in delayed clearance of Bordetella pertussis in the respiratory tract. 17) In our study, the olive oil-fed mice subjected to isolation stress showed a temporarily delayed clearance of the fungus in the liver at day 3 after infection (Table 3) and greater liver IFN-production at day 8 (Table 4) than the other three groups.…”

Toll-like receptor 2 promotes bacterial clearance during the initial stage of pulmonary infection with Acinetobacter baumannii

“…This specific response includes the release of pro-inflammatory cytokines and chemokines (8,15,16). IL-6, TNF-α, and IL-1β are representative proinflammatory cytokines and are associated with the upregulation of cell adhesion molecules and antigen presentation.…”

Identification of Ata, a Multifunctional Trimeric Autotransporter of Acinetobacter baumannii

“…Due to the overall low virulence of most A. baumannii strains in rodent models of infection, investigators have used various methods to enhance virulence, including mixing bacterial inocula with porcine mucin (49,60) or the use of neutropenic mouse models of A. baumannii infections (36,67,75). However, neutropenia is a rare clinical risk factor for patients with A. baumannii infections (1a, 6, 7, 20, 26, 34, 40, 50), and therefore an alternative model of A. baumannii infection in immunocompetent animals is desirable to more accurately mimic the types of infections caused by this organism.…”