Transcriptional profiling of host responses in mouse lungs following aerosol infection with type A Francisella tularensis
Open Access
- 1 March 2006
- journal article
- Published by Microbiology Society in Journal of Medical Microbiology
- Vol. 55 (3) , 263-271
- https://doi.org/10.1099/jmm.0.46313-0
Abstract
Tularaemia caused by inhalation of type A Francisella tularensis bacteria is one of the most aggressive infectious diseases known, but the reasons for the very rapid spread of the organism from the lungs to internal organs and the ensuing mortality are unknown. The present study used the mouse model to examine in detail the host immune response in the lung. After an aerosol challenge with 20 c.f.u. of the type A strain FSC033, all mice developed clinical signs of severe disease, showed weight loss by day 4 of infection and died the next day. Histopathological findings in the lung revealed acute inflammation and intense vasculitis and perivasculitis on day 4. Gene transcriptional changes in the mouse lung samples were examined on days 1, 2 and 4 of infection using a cDNA microarray with 20 600 mouse clones representing 18 500 genes. In total, 424 genes were found to be differentially expressed, some of which were both up- and downregulated at different time points, 192 of which were upregulated and 234 of which were downregulated for at least one time point. A high percentage of selected genes identified by the microarray analysis were confirmed to be differentially regulated by quantitative real-time PCR. Categorization of the differentially expressed genes showed that those preferentially involved in host immune responses were activated extensively on day 4 but hardly or not at all on days 1 and 2. Further analysis revealed that several of the genes upregulated on day 4 are known to depend on gamma interferon or tumour necrosis factor alpha for their regulation. In keeping with this finding, tumour necrosis factor alpha and gamma interferon levels were found to be increased significantly in bronchoalveolar lavage on day 4.Keywords
This publication has 36 references indexed in Scilit:
- Immune control of phagosomal bacteria by p47 GTPasesCurrent Opinion in Microbiology, 2005
- Tularaemia: bioterrorism defence renews interest in Francisella tularensisNature Reviews Microbiology, 2004
- TIMP3 checks inflammationNature Genetics, 2004
- TIMPs as multifacial proteinsCritical Reviews in Oncology/Hematology, 2004
- Vascular oxygen sensing: detection of novel candidates by proteomics and organ cultureJournal of Applied Physiology, 2004
- Bioenergetic Analysis of Peroxisome Proliferator-activated Receptor γ Coactivators 1α and 1β (PGC-1α and PGC-1β) in Muscle CellsJournal of Biological Chemistry, 2003
- Francisella tularensis inhibits Toll-like receptor-mediated activation of intracellular signalling and secretion of TNF-alpha and IL-1 from murine macrophagesCellular Microbiology, 2003
- Verification and initial annotation of the NIA mouse 15K cDNA clone setNature Genetics, 2001
- MECHANISMS OF PHAGOCYTOSIS IN MACROPHAGESAnnual Review of Immunology, 1999
- Aerosol infection of animals with strains ofLegionella pneumophilaof different virulence: comparison with intraperitoneal and intranasal routes of infectionEpidemiology and Infection, 1983