High susceptibility to respiratory Acinetobacter baumannii infection in A/J mice is associated with a delay in early pulmonary recruitment of neutrophils.
Acinetobacter baumannii is an important cause of both community-associated and nosocomial pneumonia, which have become increasingly difficult to treat because of the rapid development of resistance to multiple antibiotics. Despite its clinical importance, the pathogenesis of and host defense against respiratory A. baumannii infection remains largely unknown. To examine host factors that could contribute to the defense, we compared the susceptibilities of A/J and C57BL/6 mice to intranasal (i.n.) inoculation with A. baumannii. We found that A/J mice were significantly more susceptible to infection with higher mortality (P<0.05) and tissue bacterial burdens (P<0.01) as well as greater histopathology in the lung and spleen than C57BL/6 mice. More importantly, the high susceptibility of A/J mice was associated with a reduced local proinflammatory cytokine/chemokine (particularly IL-1beta, MIP-2 and TNF-alpha) responses and a significant delay and reduction in the early influx of neutrophils in the lung (P<0.05). Intranasal administration of neutrophil-inducing chemokine MIP-2 to A/J mice enhanced pulmonary neutrophil influx and partially restored host resistance to A. baumannii to a level comparable to the more resistant C57BL/6 mice. Our results imply that the early recruitment of neutrophils into the lung is critical for initiating an efficient host defense against respiratory A. baumannii infection.
Qiu
Hongyu
H
Institute for Biological Sciences, National Research Council Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada.
KuoLee
Rhonda
R
Harris
Greg
G
Chen
Wangxue
W
D000151:Acinetobacter Infections / Q000276:immunology* / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000276:immunology*; D000818:Animals; D001835:Body Weight; D054426:Chemokine CXCL2 / Q000008:administration & dosage; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D004198:Disease Susceptibility / Q000276:immunology*; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology*; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology; D012720:Severity of Illness Index; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D016019:Survival Analysis
D054426:Chemokine CXCL2; D016207:Cytokines; D007155:Immunologic Factors