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| Status |
Public on Nov 25, 2009 |
| Title |
Interferon-γ-responsive non-hematopoietic cells regulate the immune response to Mycobacterium tuberculosis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Immunity to Mycobacterium tuberculosis in humans and in mice requires interferon gamma (IFNγ). Wheras IFNγ has been studied extensively for its effects on macrophages in tuberculosis, we determined that protective immunity to tuberculosis also requires IFNγ-responsive non-hematopoietic cells. Bone marrow chimeric mice with IFNγ-unresponsive lung epithelial and endothelial cells exhibited earlier mortality and higher bacterial burdens than control mice, under-expressed indoleamine-2,3-dioxygenase (Ido1) in lung endothelium and epithelium and over-expressed interleukin-17 (IL-17) with massive neutrophilic inflammation in the lungs. We also found that the products of IDO catabolism of tryptophan selectively inhibit IL-17 production by Th17 cells, by inhibiting the action of IL-23. These results reveal a previously-unsuspected role for IFNγ responsiveness in non-hematopoietic cells in regulation of immunity to M. tuberculosis, and reveal a mechanism for IDO inhibition of Th17 cell responses.
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| Overall design |
Bone marrow chimera were created by γ-irradiation (10 Gy) of recipient mice, Ifngr+/+ (W) or Ifngr-/- (K), and reconstitution by i.v. injection of Ifngr+/+ (W) bone marrow cells. After 6 weeks, the two groups of chimera W→W and W→K were infected via the aerosol route with 100 colony forming units of Mycobacterium tuberculosis strain H37Rv. At 63 days post-infection, 4 W→W mice and 4 W→K mice were euthanized, their lung left lobe removed and processed for total RNA isolation and microarray. The 4 samples from the W→W mice were pooled together and used as control sample whereas the 4 samples from the W→K mice were pooled together and used as experimental sample. The same harvest and sample processing was conducted on day 97 after infection, using 5 W→W mice and 6 W→K mice.
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| Contributor(s) |
Desvignes L, Ernst JD |
| Citation(s) |
20064452 |
| |
| Submission date |
Nov 23, 2009 |
| Last update date |
Jan 12, 2017 |
| Contact name |
Ludovic Desvignes |
| E-mail(s) |
ludovic.desvignes@nyumc.org
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| Phone |
212-263-6785
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| Fax |
212-263-7749
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| Organization name |
New York University School of Medicine
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| Department |
Medicine
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| Lab |
Ernst
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| Street address |
522 First Avenue
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10016 |
| Country |
USA |
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| Platforms (1) |
| GPL7202 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version) |
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| Samples (2) |
| GSM474665 |
IFNgR Chimera Lung 63 Days Infection |
| GSM474668 |
IFNgR Chimera Lung 97 Days Infection |
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| Relations |
| BioProject |
PRJNA120701 |
