Defect in early lung defence against Pseudomonas aeruginosa in DBA/2 mice is associated with acute inflammatory lung injury and reduced bactericidal activity in naive macrophages.
Pseudomonas aeruginosa is an opportunistic pathogen that causes serious respiratory disease in the immune-compromised host. Using an aerosol infection model, 11 inbred mouse strains (129/Sv, A/J, BALB/c, C3H/HeN, C57BL/6, DBA/2, FVB, B10.D2/oSnJ, B10.D2/nSnJ, AKR/J and SWR/J) were tested for increased susceptibility to P. aeruginosa lung colonization. DBA/2 was the only mouse strain that had increased bacterial counts in the lung within 6 h post-infection. This deficiency incited a marked inflammatory response with reduced bacterial lung clearance and a mortality rate of 96.7 %. DBA/2 mice displayed progressive deterioration of lung pathology with extensive alveolar exudate and oedema formation at 48-72 h post-infection. The neutrophil-specific myeloperoxidase activity remained elevated throughout infection, suggesting that the increased leukocyte infiltration into alveoli caused acute inflammatory lung injury. DBA/2 mice lack the haemolytic complement; however, three additional mouse strains (AKR/J, SWR/J and A/J) with the same defect effectively cleared the infection, indicating that other host factors are involved in defence. Bone marrow-derived macrophages of DBA/2 showed an initial increase in phagocytosis, while their bactericidal activity was reduced compared to that of C57BL/6 macrophages. Comparison of pulmonary cytokine profiles of DBA/2 versus C57BL/6 or C3H/HeN indicated that DBA/2 had similar increases in tumour necrosis factor (TNF)-alpha, KC and interleukin (IL)-1a as C3H/HeN, but showed specific induction of IL-17, monocyte chemotactic protein (MCP)-1 and vascular endothelial growth factor (VEGF). Together, DBA/2 mice have a defect in the initial lung defence against P. aeruginosa colonization, which causes the host to produce a greater, but damaging, inflammatory response. Such a response may originate from the reduced antimicrobial activity of DBA/2 macrophages.
Wilson
Kari R
KR
Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine at Marshall University, Huntington, WV 25755-9320, USA.
Napper
Jennifer M
JM
Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine at Marshall University, Huntington, WV 25755-9320, USA.
Denvir
James
J
Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine at Marshall University, Huntington, WV 25755-9320, USA.
Sollars
Vincent E
VE
Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine at Marshall University, Huntington, WV 25755-9320, USA.
Yu
Hongwei D
HD
Department of Pediatrics, Joan C. Edwards School of Medicine at Marshall University, Huntington, WV 25701-3655, USA.|Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine at Marshall University, Huntington, WV 25755-9320, USA.
D000818:Animals; D003182:Complement C5 / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000254:growth & development / Q000276:immunology*; D013045:Species Specificity
D003182:Complement C5