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| Status |
Public on Feb 19, 2019 |
| Title |
Single cell analysis of diverse pathogen responses defines a molecular roadmap for generating antigen-specific immunity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The immune system generates pathogen-tailored responses. The precise innate immune cell types and pathways that direct robust adaptive immune responses have not been fully characterized. By using fluorescent pathogens combined with massively parallel single cell RNA-seq, we comprehensively characterized the initial 48 hours of the innate immune response to diverse pathogens. We found that across all pathogens tested, most of the lymph node cell types and states showed little pathogen-specificity. In contrast, the rare antigen-positive cells displayed pathogen-specific transcriptional programs as early as 24 hours after immunization. In addition, mycobacteria activated a specific NK driven IFNγ response. Depletion of NK cells and IFNγ showed that IFNγ initiated a monocyte specific signaling cascade, leading to production of major chemokines and cytokines that promote Th1 development. Our systems immunology approach sheds light on early events in innate immune responses and may help further development of safe and efficient vaccines.
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| Overall design |
Transcriptional profiling of single cells from pathogen-injected mouse auricular lymph nodes, generated from deep sequencing of thousands of cells, sequenced in several batches on illumina Nextseq500. For all experiments, innate immune lymph node cells were sorted accordng to the markers indicated in Samples' Characteristics "selection marker" field into 384-well MARS-seq2.0 cell capture plates. Sorting of antigen-carrying cells (Ag+) was based on the AF488-fluorescence of the pathogens injected. Different pathogens and time points were used, as indicated in the Samples' Characteristics "infection" and "time points" fields.
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| Contributor(s) |
Blecher-Gonen R, Bost P, Hilligan KL, David E, Salam TM, Roussel E, Connor LM, Mayer JU, Halpern KB, Tóth B, Itzkovitz S, Schwikowski B, Ronchese F, Amit I |
| Citation(s) |
30772378 |
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| Submission date |
Jan 14, 2019 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Ido Amit |
| E-mail(s) |
ido.amit@weizmann.ac.il
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| Phone |
972-8-9343338
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| Organization name |
Weizmann Institute of Science
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| Department |
Immunology
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| Street address |
234 Herzl st.
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| City |
Rehovot |
| ZIP/Postal code |
760001 |
| Country |
Israel |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (91)
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| Relations |
| BioProject |
PRJNA515047 |
| SRA |
SRP179081 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE125044_RAW.tar |
54.5 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE125044_metadata.txt.gz |
256.7 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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