Affiliation:
1. Institute for Biological Sciences, National Research Council Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada
Abstract
ABSTRACT
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
.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
59 articles.
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