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| Status |
Public on Nov 06, 2018 |
| Title |
Induction of autonomous memory alveolar macrophages requires T-cell help and is critical to trained immunity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Innate immune memory is a new important area of research. However, innate immune memory at the major mucosal sites remains poorly understood. Here we show that respiratory viral infection induces long-lasting memory alveolar macrophages (AM). Memory AM are programed to express high MHC II, carry a defense-ready gene signature, and produce, upon re-stimulation, neutrophil chemokines. Using a multitude of approaches, we reveal that the priming, but not maintenance, of memory AM requires the help from effector CD8 T cells. T cells jump-start this process in AM via IFN-γ production. We further find that formation/maintenance of memory AM are independent of monocytes or bone marrow progenitors. Finally, we demonstrate that memory AM are poised for robust trained immunity against bacterial infection in the lung via rapid induction of chemokines and neutrophilia. Our study thus establishes a new paradigm of immunological memory formation whereby adaptive T-lymphocytes render innate memory of mucosal-associated macrophages.
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| Overall design |
Acute respiratory viral infection was elicited by intranasal inoculation with a recombinant human serotype 5 adenovirus expressing an Mtb protein Ag85A at 5×107 PFU per mouse. PBS inoculated mice were used as control. At 4 weeks post infection, CD11b-CD11c+ alveolar macrophages (AM) were purified from bronchoalveolar lavage fluid by using magnetic selection. AM from each 3 mice were pooled and used as one sample and triplicate samples/group were set up for RNA extraction and gene microarray analysis. Quality of RNA and subsequent microarray was carried out by the Center for Applied Genomics of The Hospital for Sick Children (Toronto, ON). The quality of RNA samples was analyzed using the Agilent 2100 bioanalyzer, which uses RNA 6000 Nano LabChip platform (Agilent Technologies Canada, Mississauga, ON). RNA samples were then subjected to RNA microarray expression analysis using the Affymetrix Mouse Gene 2.0 ST array. This array contains protein-coding regions.
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| Web link |
https://doi.org/10.1016/j.cell.2018.09.042
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| Contributor(s) |
Yao Y, Jeyanathan M, Haddadi S, Barra NG, Vaseghi-Shanjani M, Damjanovic D, Lai R, Afkhami S, Chen Y, Dvorkin-Gheva A, Robbins CS, Schertzer JD, Xing Z |
| Citation(s) |
30433869, 36456739 |
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| Submission date |
Aug 14, 2018 |
| Last update date |
Jan 06, 2023 |
| Contact name |
Zhou Xing |
| E-mail(s) |
xingz@mcmaster.ca
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| Organization name |
McMaster University
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| Department |
Pathology and Molecular Medicine
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| Lab |
MDCL-4084
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| Street address |
1280 Main Street West
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| City |
Hamilton |
| State/province |
Ontario |
| ZIP/Postal code |
L8S4K1 |
| Country |
Canada |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| GSM3331335 |
Alveolar macrophages d28 post Ad infection rep1 |
| GSM3331336 |
Alveolar macrophages d28 post Ad infection rep2 |
| GSM3331337 |
Alveolar macrophages d28 post Ad infection rep3 |
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| Relations |
| BioProject |
PRJNA485891 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE118512_RAW.tar |
54.3 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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