Project name: Mus musculus

Description: Bacterial infections and cigarette smoking have been linked to exacerbations of respiratory disease including severe asthma and chronic obstructive pulmonary disease (COPD). Epidemiological studies have also shown increased incidences of respiratory tract infections even in young smokers. We have previously shown that cigarette smoke exacerbates the inflammatory response to influenza A virus (PLoS ONE. 2010 Oct 12;5(10): e13251) and nontypeable Haemophilus influenzae (Am J Respir Crit Care Med. 2009 Apr 15;179(8):666) infection. While it is well understood that cigarette smoke impairs respiratory host defense, little is known with respect to mechanisms driving the outcome of infection in smoke-exposed mice. In this study, we attempt to characterize the antibacterial responses of lung resident cells from smoke-exposed mice to TLR agonists and live pathogens by gene expression profiling and to compare similarities and differences of inflammatory profiles between mouse and man.Overall design: C57BL/6 mice were exposed to room air or cigarette smoke for four days. Mice were exposed to twelve cigarettes (2R4 reference cigarettes; Tobacco and Health Research Institute, University of Kentucky), twice daily in a whole body smoke exposure system (SIU48, PROMECH LAB AB, Vintrie, Sweden). Mice were subsequently euthanized and the lungs inflated with a low-gelling agarose. 120 μm precision cut lung slices (PCLS) were generated. PCLS from room-air and cigarette smoke exposed mice were stimulated ex vivo with TLR agonists (Pam3CSK for TLR2, LPS for TLR4), as well as live and heat-killed versions of Hemophilus Influenza and S. Pneumoniae. Samples were collected 6h, 12h and 24h post-stimulation for gene expression profiling.

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: ModelOrganism

Last updated: 2012-10-18