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| Status |
Public on Oct 25, 2018 |
| Title |
Invasive non-typhoidal Salmonella dysregulates the repertoire of dendritic cell responses to intracellular and extracellular stimuli [bulk RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Non-typhoidal Salmonella (NTS) are among of the most important food-borne pathogens. Recently, a highly invasive multi-drug resistant S. Typhimurium of a distinct multilocus sequence type (MLST), ST313, has emerged across sub-Saharan Africa as a major cause of lethal bacteraemia in children and immunosuppressed adults. Encounters between dendritic cells (DCs) and invading bacteria determine the course of infection but whether or how ST313 might usurp DC mediated defence has not been reported. Here we utilised fluorescently labelled invasive and non-invasive strains of Salmonella combined with single-cell RNA sequencing to study the transcriptomes of individual infected and bystander DCs. The transcriptomes displayed a repertoire of cell instrinsic and extrinsic innate response states that differed between invasive and non-invasive strains. Gene expression heterogeneity was increased in DCs challenged with invasive Salmonella. DCs exposed but not harbouring invasive Salmonella exhibited a hyper-activated profile that likely facilitates trafficking of infected cells and dissemination of internalised intact bacteria. In contrast, invasive Salmonella containing DCs demonstrate reprogramming of trafficking genes required to avoid autophagic destruction. Furthermore, these cells displayed differential expression of tolerogenic IL10 and MARCH1 enabling CD83 mediated adaptive immune evasion. Altogether our data illustrate pathogen cell-to cell variability directed by a Salmonella invasive strain highlighting potential mechanisms of host adaption with implications for dissemination in vivo.
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| Overall design |
RNA-seq of mini-bulks (5000 cells) of human monocyte derived dendritic cells infected with S. Typhimurium strain LT2 or D23580 or left uninfected
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| Contributor(s) |
Aulicino A, Rue-Albrecht K, Preciado-llanes L, Napolitani G, Ambrose T, Ashley N, Cribbs A, Gordon M, Sims D, Simmons A |
| Citation(s) |
30451854 |
| |
| Submission date |
Mar 07, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Anna Aulicino |
| E-mail(s) |
anna.aulicino@ndm.ox.ac.uk
|
| Organization name |
University of Oxford
|
| Department |
Human Immunology Unit, WIMM
|
| Street address |
Headley Way, Headington
|
| City |
Oxford |
| State/province |
Oxfordshire |
| ZIP/Postal code |
OX3 9DU |
| Country |
United Kingdom |
| |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
|
| Samples (45)
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| This SubSeries is part of SuperSeries: |
| GSE111546 |
Invasive non-typhoidal Salmonella dysregulates the repertoire of dendritic cell responses to intracellular and extracellular stimuli |
|
| Relations |
| BioProject |
PRJNA437330 |
| SRA |
SRP134128 |
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