Invasive Salmonella Exploits Divergent Immune Evasion Strategies in Infected and Bystander Dendritic Cell Subsets

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Nov 20

PMID 30451854

Citations 12

Authors

Anna Aulicino

Kevin C Rue-Albrecht

Lorena Preciado-Llanes

Giorgio Napolitani

Neil Ashley

Adam Cribbs

Jana Koth

B Christoffer Lagerholm

Tim Ambrose

Melita A Gordon

David Sims

Alison Simmons

Affiliations

Soon will be listed here.

Abstract

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.

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