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Invasive non-typhoidal Salmonella dysregulates the repertoire of dendritic cell responses to intracellular and extracellular stimuli [scRNA-seq]

ABSTRACT: Invasive non-typhoidal Salmonella dysregulates the repertoire of dendritic cell responses to intracellular and extracellular stimuli [scRNA-seq]

PROVIDER: PRJNA437328 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6815590_1.fastq.gz	Fastqsanger.gz
	SRR6815590_2.fastq.gz	Fastqsanger.gz
	SRR6815600_1.fastq.gz	Fastqsanger.gz
	SRR6815600_2.fastq.gz	Fastqsanger.gz
	SRR6815610_1.fastq.gz	Fastqsanger.gz

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Invasive non-typhoidal Salmonella dysregulates the repertoire of dendritic cell responses to intracellular and extracellular stimuli

Project description:Invasive non-typhoidal Salmonella dysregulates the repertoire of dendritic cell responses to intracellular and extracellular stimuli

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Invasive non-typhoidal Salmonella dysregulates the repertoire of dendritic cell responses to intracellular and extracellular stimuli [bulk RNA-seq]

Project description:Invasive non-typhoidal Salmonella dysregulates the repertoire of dendritic cell responses to intracellular and extracellular stimuli [bulk RNA-seq]

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Invasive non-typhoidal Salmonella dysregulates the repertoire of dendritic cell responses to intracellular and extracellular stimuli [scRNA-seq]

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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Invasive non-typhoidal Salmonella dysregulates the repertoire of dendritic cell responses to intracellular and extracellular stimuli

Project description:This SuperSeries is composed of the SubSeries listed below.

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Project description:Salmonella enterica represent a major disease burden worldwide. While non-typhoidal Salmonella (NTS) serovars trigger self-limiting diarrhoea, leading to occasional secondary bacteraemia, S. enterica serovar Typhi is responsible for potentially life-threatening Typhoid fever. Dendritic cells (DCs) are key professional antigen presenting cells of the human immune system. The ability of pathogenic bacteria to subvert DC functions and prevent T cell recognition contributes to their survival and dissemination within the host. Here, we adapted Dual RNA-sequencing to define how different Salmonella pathovariants remodel their gene expression in tandem with that of infected DCs. We find DCs harness iron handling pathways to defend against invading Salmonellas, which, the human pathogen S. Typhi is able to circumvent. We show that S. Typhi mounts a robust response to host oxidative stress to avoid host iron-mediated defence mechanisms. In parallel, we provide evidence that invasive non-typhoidal Salmonella employs several strategies to impair DC functions and undertake alternative nutrient scavenging strategies to survive in the hostile intracellular environment.

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