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Non-typhoidal  Salmonella  (NTS) are highly prevalent food-borne pathogens. Recently, a highly invasive, multi-drug resistant  S . Typhimurium, ST313, emerged as a major cause of bacteraemia in children and immunosuppressed adults, however the pathogenic mechanisms remain unclear. Here, we utilize invasive and non-invasive  Salmonella  strains combined with single-cell RNA-sequencing to study the transcriptome of individual infected and bystander monocyte-derived dendritic cells (MoDCs) implicated in disseminating invasive ST313. Compared with non-invasive  Salmonella , ST313 directs a highly heterogeneous innate immune response. Bystander MoDCs exhibit a hyper-activated profile potentially diverting adaptive immunity away from infected cells. MoDCs harbouring invasive  Salmonella  display higher expression of  IL10  and  MARCH1  concomitant with lower expression of  CD83  to evade adaptive immune detection. Finally, we demonstrate how these mechanisms conjointly restrain MoDC-mediated activation of  Salmonella -specific CD4 +  T cell clones. Here, we show how invasive ST313 exploits discrete evasion strategies within infected and bystander MoDCs to mediate its dissemination in vivo.

Invasive Salmonella exploits divergent immune evasion strategies in infected and bystander dendritic cell subsets