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| Status |
Public on Jan 27, 2011 |
| Title |
Gene expression in mouse lung epithelial cells treated with synthetic TLR ligands to induce resistance |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Infectious pneumonias exact an unacceptable mortality burden worldwide. Efforts to protect populations from pneumonia have historically focused on antibiotic development and vaccine-enhanced adaptive immunity. However, we have recently reported that the lungs’ innate defenses can be therapeutically induced by inhalation of a bacterial lysate that protects mice against otherwise lethal pneumonia. Here, we tested in mice the hypothesis that Toll-like receptors (TLRs) are required for this antimicrobial phenomenon, and found that resistance could not be induced in the absence of the TLR signaling adaptor protein MyD88. We then attempted to recapitulate the protection afforded by the bacterial lysate by stimulating the lung epithelium with aerosolized synthetic TLR ligands. While most single or combination treatments yielded no protection, simultaneous treatment with ligands for TLR2/6 and TLR9 conferred robust, synergistic protection against virulent Gram-positive and Gram-negative pathogens. Protection was associated with rapid pathogen killing in the lungs, and pathogen killing could be induced from lung epithelial cells in isolation. Taken together, these data demonstrate the requirement for TLRs in inducible resistance against pneumonia, reveal a remarkable, unanticipated synergistic interaction of TLR2/6 and TLR9, reinforce the emerging evidence supporting the antimicrobial capacity of the lung epithelium, and may provide the basis for a novel clinical therapeutic that can protect patients against pneumonia during periods of peak vulnerability.
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| Overall design |
MLE-15 cells were treated with 20 ul volumes of PBS (sham treatment), ODN2395 (0.4 ug), Pam2CSK4 (0.2 ug) or ODN2395+Pam2CSK4. At least 5 unique samples per group. Treated for 2 hours. Hybridized to Illumina Sentrix MouseRef-8 v2 Beadhips.
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| Citation(s) |
21482737, 22299046, 23632328 |
| Submission date |
Jan 25, 2011 |
| Last update date |
Oct 25, 2019 |
| Contact name |
Scott E Evans |
| E-mail(s) |
seevans@mdanderson.org
|
| 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 |
| |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (22)
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| Relations |
| BioProject |
PRJNA135993 |
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