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Series GSE13740 Query DataSets for GSE13740
Status Public on Nov 26, 2008
Title Gene expression in C57BL/6 mouse lungs after exposure to aerosolized NTHi lysate
Organism Mus musculus
Experiment type Expression profiling by array
Summary Pneumonia is a serious problem worldwide. We recently demonstrated that innate defense mechanisms of the lung are highly inducible against pneumococcal pneumonia. To determine the breadth of protection conferred by stimulation of lung mucosal innate immunity, and to identify cells and signaling pathways activated by this treatment, mice were treated with an aerosolized bacterial lysate, then challenged with lethal doses of bacterial and fungal pathogens. Mice were highly protected against a broad array of Gram-positive, Gram-negative, and Class A bioterror bacterial pathogens, and Aspergillus fumigatus. Protection was associated with rapid pathogen killing within the lungs, and this effect was recapitulated in vitro using a respiratory epithelial cell line. Gene expression analysis of lung tissue showed marked activation of NF-kappaB, Type I and II interferon, and antifungal Card9-Bcl10-Malt1 pathways. Cytokines were the most strongly induced genes, but the inflammatory cytokines TNF and IL-6 were not required for protection. Lung-expressed antimicrobial peptides were also highly upregulated. Taken together, stimulated innate resistance (StIR) appears to occur through the activation of multiple host defense signaling pathways in lung epithelial cells, inducing rapid pathogen killing, and conferring broad protection against virulent bacterial and fungal pathogens. Augmentation of innate antimicrobial defenses of the lungs might have therapeutic value for protection of patients with neutropenia or impaired adaptive immunity against opportunistic pneumonia, and for defense of immunocompetent subjects against a bioterror threat or epidemic respiratory infection.

Keywords: differential gene expression; time course; innate immunity; pneumonia; immunocompromised host; lung epithelium
Overall design Gene expression patterns in mouse lung homogenates were analyzed 2h after exposure to aerosolized PBS (Sham treatment), 2h after exposure to aerosolized NTHi lysate or 4h after exposure to aerosolized NTHi lysate. Each group consisted of six mice.
Contributor(s) Evans S
Citation(s) 19137067
Submission date Nov 25, 2008
Last update date Jan 18, 2013
Contact name Scott E Evans
Organization name University of Texas-M.D. Anderson Cancer Center
Department Pulmonary Medicine - Box 403
Street address 1400 Holcombe Blvd
City Houston
State/province TX
ZIP/Postal code 77030
Country USA
Platforms (1)
GPL6105 Illumina mouse-6 v1.1 expression beadchip
Samples (18)
GSM345353 Sham; 1740174013_A
GSM345354 Sham; 1740174013_D
GSM345355 Sham; 1740174047_A
BioProject PRJNA109389

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE13740_RAW.tar 5.2 Mb (http)(custom) TAR
GSE13740_Unnormalized_Data.txt 17.9 Mb (ftp)(http) TXT
Processed data included within Sample table

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