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| Status |
Public on Dec 23, 2022 |
| Title |
Bacteria hijack a neuro-immune axis in meninges to facilitate brain invasion |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The meninges are densely innervated by nociceptive sensory neurons that mediate pain and headache. How pain and neuro-immune interactions impact meningeal host defenses is unclear. Bacterial meningitis causes life-threatening infections of the meninges and central nervous system (CNS), affecting over one million people a year. Here we find that Nav1.8+ neuron signaling to immune cells in the meninges via the neuropeptide calcitonin gene-related peptide (CGRP) exacerbates bacterial meningitis. Nociceptor ablation reduced meningeal and brain invasion by two bacterial pathogens: Streptococcus pneumoniae and Streptococcus agalactiae. S. pneumoniae activated nociceptors via Pneumolysin to release CGRP, which acts through its receptor RAMP1 on meningeal macrophages to inhibit chemokine expression, neutrophil recruitment and antimicrobial defenses. Macrophage-specific RAMP1 deficiency or blockade of RAMP1 signaling enhanced immune responses and bacterial clearance in meninges and brain. Therefore, targeting a neuro-immune axis in the meninges can enhance host defenses and may be a potential treatment for bacterial meningitis.
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| Overall design |
For in vitro bulk RNA-seq experiments, there are 24 samples total, representing 4 biological replicates, two technical replicates, of 3 conditions at 1 time point. For in vivo scRNA-seq experiments, there are 40 samples total, representing 10 biological replicates of 4 conditions at 1 time point.
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| Contributor(s) |
Pinho-Ribeiro FA, Deng L, Neel DV, Erdogan O, Basu H, Yang D, Choi S, Walker AJ, Carneiro-Nascimento S, He K, Wu G, Stevens B, Doran K, Levy D, Chiu I |
| Citation(s) |
36859544 |
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| Submission date |
Dec 23, 2022 |
| Last update date |
Mar 17, 2023 |
| Contact name |
Felipe Almeida de Pinho Ribeiro |
| E-mail(s) |
dfelipe@wustl.edu
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| Phone |
8572658909
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| Organization name |
Washington University in St Louis
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| Street address |
4515 McKinley Ave
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| City |
St Louis |
| State/province |
MO |
| ZIP/Postal code |
63110 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (31)
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| Relations |
| BioProject |
PRJNA915369 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE221681_StrepCGRP_filtered_feature_bc_matrix.h5 |
36.0 Mb |
(ftp)(http) |
H5 |
| GSE221681_Strep_filtered_feature_bc_matrix.h5 |
33.4 Mb |
(ftp)(http) |
H5 |
| GSE221681_Vehicle_filtered_feature_bc_matrix.h5 |
30.3 Mb |
(ftp)(http) |
H5 |
| GSE221681_filtered_feature_bc_matrix.h5 |
32.8 Mb |
(ftp)(http) |
H5 |
| GSE221681_tx2gene.rda.gz |
1.2 Mb |
(ftp)(http) |
RDA |
| GSE221681_txi.rda.gz |
52.5 Mb |
(ftp)(http) |
RDA |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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