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

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 invas...

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Main Authors: Aulicino, A, Rue-Albrecht, K, Preciado-Llanes, L, Napolitani, G, Ashley, N, Cribbs, A, Koth, J, Lagerholm, B, Ambrose, T, Gordon, M, Sims, D, Simmons, A
格式: Journal article
語言:English
出版: Springer Nature 2018
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author Aulicino, A
Rue-Albrecht, K
Preciado-Llanes, L
Napolitani, G
Ashley, N
Cribbs, A
Koth, J
Lagerholm, B
Ambrose, T
Gordon, M
Sims, D
Simmons, A
author_facet Aulicino, A
Rue-Albrecht, K
Preciado-Llanes, L
Napolitani, G
Ashley, N
Cribbs, A
Koth, J
Lagerholm, B
Ambrose, T
Gordon, M
Sims, D
Simmons, A
author_sort Aulicino, A
collection OXFORD
description 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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spelling oxford-uuid:ac439813-9398-43ae-ac95-098fe42579572022-03-27T03:27:46ZInvasive Salmonella exploits divergent immune evasion strategies in infected and bystander dendritic cell subsetsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ac439813-9398-43ae-ac95-098fe4257957EnglishSymplectic Elements at OxfordSpringer Nature2018Aulicino, ARue-Albrecht, KPreciado-Llanes, LNapolitani, GAshley, NCribbs, AKoth, JLagerholm, BAmbrose, TGordon, MSims, DSimmons, ANon-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.
spellingShingle Aulicino, A
Rue-Albrecht, K
Preciado-Llanes, L
Napolitani, G
Ashley, N
Cribbs, A
Koth, J
Lagerholm, B
Ambrose, T
Gordon, M
Sims, D
Simmons, A
Invasive Salmonella exploits divergent immune evasion strategies in infected and bystander dendritic cell subsets
title Invasive Salmonella exploits divergent immune evasion strategies in infected and bystander dendritic cell subsets
title_full Invasive Salmonella exploits divergent immune evasion strategies in infected and bystander dendritic cell subsets
title_fullStr Invasive Salmonella exploits divergent immune evasion strategies in infected and bystander dendritic cell subsets
title_full_unstemmed Invasive Salmonella exploits divergent immune evasion strategies in infected and bystander dendritic cell subsets
title_short Invasive Salmonella exploits divergent immune evasion strategies in infected and bystander dendritic cell subsets
title_sort invasive salmonella exploits divergent immune evasion strategies in infected and bystander dendritic cell subsets
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