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GEO help: Mouse over screen elements for information. |
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Status |
Public on Dec 31, 2016 |
Title |
Impaired calcineurin signaling in dendritic cells and macrophages increases susceptibility to aspergillosis through pentraxin-3 downregulation |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Treatment of post-transplant patients with immunosuppressive drugs targeting the calcineurin-NFAT pathway, such as Cyclosporine A or Tacrolimus, are commonly associated with a higher incidence of opportunistic infections, such as Aspergillus fumigatus, which can lead to severe life-threating conditions. A component of the A. fumigatus cell wall, β-glucan, is recognized by dendritic cells via the Dectin-1 receptor, triggering downstream signaling that leads to calcineurin-NFAT binding, NFAT translocation, and transcription of NFAT-regulated genes. Here, we address the question of whether calcineurin signaling in CD11c-expressing cells, such as DCs, has a specific role in the innate control of A. fumigatus. Impairment of calcineurin in CD11c-expressing cells (CD11ccrecnb1loxP) significantly increased susceptibility to systemic A. fumigatus infection and to intranasal infection in irradiated mice undergoing bone marrow transplant. Global expression profiling of bone marrow-derived DCs identified calcineurin-regulated processes in the immune response to infection, including expression of pentraxin-3, an important anti-fungal defense protein. These results suggest that calcineurin inhibition directly impairs important immunoprotective functions of myeloid cells, as shown by the higher susceptibility of CD11ccrecnbloxP mice in models of systemic and invasive pulmonary aspergillosis, including after allogeneic bone marrow transplantation. These findings are relevant to the clinical management of transplant patients with severe Aspergillus infections.
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Overall design |
Conditional calcineurin knock-out bone marrow-derived dendritic cells and their littermates controls were stimulated with Aspergillus fumigatus morphotypes in order to identify genes regulated through calcineurin signaling.
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Contributor(s) |
Fric J, Zelante T, Wong AY, Mencarelli A, Koh G, Zolezzi F, Lee B, Poidinger M, Ricciardi-Castagnoli P |
Citation(s) |
27301880 |
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Submission date |
Aug 11, 2015 |
Last update date |
Mar 04, 2019 |
Contact name |
Bernett Lee |
E-mail(s) |
bernett_lee@immunol.a-star.edu.sg
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Organization name |
Singapore Immunology Network
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Street address |
8A Biomedical Grove #03-06 Immunos
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City |
NA |
ZIP/Postal code |
138648 |
Country |
Singapore |
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Platforms (1) |
GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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Samples (18)
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GSM1847588 |
Sample 731/6, wild type DC stimulated with conidia |
GSM1847589 |
Sample 731/7, wild type DC stimulated with swollen conidia |
GSM1847590 |
Sample 731/8, wild type DC stimulated with hyphae |
GSM1847591 |
Sample 584/6, wild type DC stimulated with conidia |
GSM1847592 |
Sample 584/7, wild type DC stimulated with swollen conidia |
GSM1847593 |
Sample 584/8, wild type DC stimulated with hyphae |
GSM1847594 |
Sample 586/6, wild type DC stimulated with conidia |
GSM1847595 |
Sample 586/7, wild type DC stimulated with swollen conidia |
GSM1847596 |
Sample 586/8, wild type DC stimulated with hyphae |
GSM1847597 |
Sample 591/6, knockout DC stimulated with conidia |
GSM1847598 |
Sample 591/7, knockout DC stimulated with swollen conidia |
GSM1847599 |
Sample 591/8, knockout DC stimulated with hyphae |
GSM1847600 |
Sample 592/6, knockout DC stimulated with conidia |
GSM1847601 |
Sample 592/7, knockout DC stimulated with swollen conidia |
GSM1847602 |
Sample 592/8, knockout DC stimulated with hyphae |
GSM1847603 |
Sample 593/6, knockout DC stimulated with conidia |
GSM1847604 |
Sample 593/7, knockout DC stimulated with swollen conidia |
GSM1847605 |
Sample 593/8, knockout DC stimulated with hyphae |
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Relations |
BioProject |
PRJNA292504 |
Supplementary file |
Size |
Download |
File type/resource |
GSE71936_RAW.tar |
78.0 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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