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)-α, 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.; Napper,, Jennifer M.; Denvir, James; Sollars, Vincent E.; and Yu, Hongwei D., "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" (2007). Biochemistry and Microbiology. 2.