Non-typhoidal Salmonella from the Gambia
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB38968 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| CAIZAB01.dat.gz | Other | |||
| CAIZAB01.fasta.gz | Fasta.gz | |||
| CAIZAB01.master.dat | Other | |||
| CAIZAC01.dat.gz | Other |
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Project description: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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Project description: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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