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| Status |
Public on May 20, 2024 |
| Title |
Transcriptional profiling links unique human macrophage phenotypes to the growth of intracellular Salmonella enterica serovar Typhi |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Macrophages provide a crucial environment for Salmonella enterica serovar Typhi (S. Typhi) to multiply during typhoid fever, yet our understanding of how human macrophages and S. Typhi interact remains limited. In this study, we delve into the dynamics of S. Typhi replication within human macrophages and the resulting heterogeneous transcriptomic responses of macrophages during infection. Our study reveals key factors that influence macrophage diversity, uncovering distinct immune and metabolic pathways associated with different stages of S. Typhi intracellular replication in macrophages. Of note, we found that macrophages harboring replicating S. Typhi are skewed towards an M1 pro-inflammatory state, whereas macrophages containing non-replicating S. Typhi exhibit neither a distinct M1 pro-inflammatory nor M2 anti-inflammatory state. Additionally, macrophages with replicating S. Typhi were characterized by the increased expression of genes associated with STAT3 phosphorylation and the activation of the STAT3 transcription factor. Our results shed light on transcriptomic pathways involved in the susceptibility of human macrophages to intracellular S. Typhi replication, thereby providing crucial insight into host phenotypes that restrict and support S. Typhi infection.
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| Overall design |
To investigate heterogeneity in human macrophage responses to intracellular S. Typhi infection, macrophages were sorted based on intracellular bacterial phenotypes (i.e. replicating, non-replicating, killed by the host), and RNA was isolated from the sorted cells for RNA-Seq.
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| Contributor(s) |
Schade R, Butler DS, McKenna JA, Di Luccia B, Shokoohi V, Hamblin M, Pham TH, Monack DM |
| Citation(s) |
38834738 |
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| Submission date |
May 20, 2024 |
| Last update date |
Jun 26, 2024 |
| Contact name |
Denise Monack |
| E-mail(s) |
dmonack@stanford.edu
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| Organization name |
Stanford University
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| Department |
Microbiology and Immunology
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| Lab |
Denise Monack
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| Street address |
299 Campus Drive, Fairchild Building D331
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| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (18)
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| GSM8281291 |
Replicating, biol rep 1 |
| GSM8281292 |
Replicating, biol rep 2 |
| GSM8281293 |
Replicating, biol rep 3 |
| GSM8281294 |
Host Killed, biol rep 1 |
| GSM8281295 |
Host Killed, biol rep 2 |
| GSM8281296 |
Host Killed, biol rep 3 |
| GSM8281297 |
Mixed, biol rep 1 |
| GSM8281298 |
Mixed, biol rep 2 |
| GSM8281299 |
Mixed, biol rep 3 |
| GSM8281300 |
Non Replicating, biol rep 1 |
| GSM8281301 |
Non Replicating, biol rep 2 |
| GSM8281302 |
Non Replicating, biol rep 3 |
| GSM8281303 |
Uninfected, biol rep 1 |
| GSM8281304 |
Uninfected, biol rep 2 |
| GSM8281305 |
Uninfected, biol rep 3 |
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| Relations |
| BioProject |
PRJNA1113598 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE267899_mRNA.transcripts_TPM.txt.gz |
5.5 Mb |
(ftp)(http) |
TXT |
| GSE267899_raw_gene_counts.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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