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| Status |
Public on Nov 21, 2008 |
| Title |
Gene expression in respiratory epithelial cells treated to induce StIR |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| 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-kappa-B, 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 expression, innate immunity, pneumonia, immunocompromised host; lung epithelium, in vitro,
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| Overall design |
MLE-15 cells were treated with sham (PBS), NTHi lysate (100 ug/ml) or EF2505-III (40 ug/ml). 4 unique samples per group. Treated for 2 hours. Hybridized to Illumina Sentrix Mouse-6 v1.1 Beadhips.
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| Citation(s) |
19329554 |
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| Submission date |
Nov 20, 2008 |
| Last update date |
Jan 18, 2013 |
| Contact name |
Scott E Evans |
| E-mail(s) |
seevans@mdanderson.org
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| Organization name |
University of Texas-M.D. Anderson Cancer Center
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| Department |
Pulmonary Medicine - Unit 1462
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| Street address |
1400 Holcombe Blvd
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| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
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| Platforms (1) |
| GPL6105 |
Illumina mouse-6 v1.1 expression beadchip |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA110439 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE13685_RAW.tar |
5.2 Mb |
(http)(custom) |
TAR |
| GSE13685_raw_intensities.txt |
16.4 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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