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
- 1 April 2007
- journal article
- Published by Microbiology Society in Microbiology
- Vol. 153 (4), 968-979
- https://doi.org/10.1099/mic.0.2006/002261-0
Abstract
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.Keywords
This publication has 33 references indexed in Scilit:
- SHIP Represses the Generation of Alternatively Activated MacrophagesImmunity, 2005
- A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17Nature Immunology, 2005
- Phagocytosis of Apoptotic Neutrophils Regulates Granulopoiesis via IL-23 and IL-17Immunity, 2005
- Three Different Neutrophil Subsets Exhibited in Mice with Different Susceptibilities to Infection by Methicillin-Resistant Staphylococcus aureusImmunity, 2004
- Alternative activation of macrophagesNature Reviews Immunology, 2003
- EFFECTS OF Cl2MDP-ENCAPSULATING LIPOSOMES IN A MURINE MODEL OFPSEUDOMONAS AERUGINOSA-INDUCED SEPSISJournal of Liposome Research, 2002
- Innate Lung Defenses and CompromisedPseudomonas aeruginosaClearance in the Malnourished Mouse Model of Respiratory Infections in Cystic FibrosisInfection and Immunity, 2000
- Isolation of Murine MacrophagesCurrent Protocols in Immunology, 1994
- Measurement of Cutaneous Inflammation: Estimation of Neutrophil Content with an Enzyme MarkerJournal of Investigative Dermatology, 1982
- Genetics of MuBl and of a complement defect in inbred strains of miceGenetics Research, 1966