%0 Journal Article %A Wilson, Kari R %A Napper, Jennifer M %A Denvir, James %A Sollars, Vincent E %A Yu, Hongwei D %T Defect in early lung defence against Pseudomonas aeruginosa in DBA/2 mice is associated with acute inflammatory lung injury and reduced bactericidal activity in naïve macrophages %D 2007 %J Microbiology, %V 153 %N 4 %P 968-979 %@ 1465-2080 %R https://doi.org/10.1099/mic.0.2006/002261-0 %K IL, interleukin %K H&E, haematoxylin and eosin %K C3, mouse strain C3H/HeN %K MIP, macrophage inflammatory protein %K TNF, tumour necrosis factor %K D2, mouse strain DBA/2 %K MPO, myeloperoxidase %K B6, mouse strain C57BL/6 %K ALI, acute lung injury %I Microbiology Society, %X 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. %U https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.2006/002261-0