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| Status |
Public on Jun 01, 2019 |
| Title |
Combined phosphoproteome and transcriptome analysis of the macrophage response to mycobacterial cord factor reveals a dichotomy of MINCLE-dependent and -independent signaling |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Immune sensing of Mycobacterium tuberculosis relies on recognition by macrophages. Mycobacterial cord factor, trehalose-6,6’-dimycolate (TDM), is the most abundant cell wall glycolipid and binds to the C-type lectin receptor (CLR) MINCLE. To explore the kinase signaling linking the TDM-MINCLE interaction to gene expression, we employed quantitative phosphoproteome analysis. TDM caused upregulation of 6.7% and suppressed 3.8% of the 14,000 phospho-sites identified on 3727 proteins. MINCLE-dependent phosphorylation was observed for canonical players of CLR signaling (e.g. PLCg, PKCd), and was enriched for PKCd and GSK3 kinase motifs. MINCLE-dependent activation of the PI3K-AKT-GSK3 pathway contributed to inflammatory gene expression and required the PI3K regulatory subunit p85a. Unexpectedly, a substantial fraction of TDM-induced phosphorylation was MINCLE-independent, a finding paralleled by transcriptome data. Bioinformatic analysis of both datasets concurred in the requirement for MINCLE for innate immune response pathways and processes. In contrast, MINCLE-independent phosphorylation and transcriptome responses were linked to cell cycle regulation. Collectively, our global analyses show substantial reprogramming of macrophages by TDM and reveal a dichotomy of MINCLE-dependent and -independent signaling linked to distinct biological responses.
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| Overall design |
mRNA profiles from TDM stimulated and unstimulated wildtype and Mincle-/- BMDM were generated by RNASeq (8 samples, duplicates from independent experiments, for each sample RNA was pooled from biological replicates, controls: unstimulated BMDM and solvent controls)
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| Contributor(s) |
Hansen M, Killy B, Büttner C, Ekici A, Lang R |
| Citation missing |
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| |
| Submission date |
Jun 04, 2018 |
| Last update date |
Jun 01, 2019 |
| Contact name |
Steffen Uebe |
| E-mail(s) |
steffen.uebe@uk-erlangen.de
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| Phone |
+49-9131-85-26101
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| Organization name |
Universitaetsklinikum Erlangen
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| Department |
Humangenetisches Institut
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| Street address |
Schwabachanlage 10
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| City |
Erlangen |
| ZIP/Postal code |
91054 |
| Country |
Germany |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA474533 |
| SRA |
SRP149734 |
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