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Series GSE71936 Query DataSets for GSE71936
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
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.
 
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.
 
Contributor(s) Fric J, Zelante T, Wong AY, Mencarelli A, Koh G, Zolezzi F, Lee B, Poidinger M, Ricciardi-Castagnoli P
Citation(s) 27301880
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
Organization name Singapore Immunology Network
Street address 8A Biomedical Grove #03-06 Immunos
City NA
ZIP/Postal code 138648
Country Singapore
 
Platforms (1)
GPL6246 [MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version]
Samples (18)
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
Relations
BioProject PRJNA292504

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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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