Aulicino, Anna, Rue-Albrecht, Kevin C, Preciado-Llanes, Lorena, Napolitani, Giorgio, Ashley, Neil, Cribbs, Adam, Koth, Jana, Lagerholm, B Christoffer, Ambrose, Tim, Gordon, Melita A 
ORCID: 0000-0002-0629-0884 et al (show 2 more authors)
(2018)
Invasive Salmonella exploits divergent immune evasion strategies in infected and bystander dendritic cell subsets.
NATURE COMMUNICATIONS, 9 (1).
4883-.
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Dendritic Cells, CD4-Positive T-Lymphocytes, Monocytes, Humans, Salmonella typhimurium, Ubiquitin-Protein Ligases, Immunoglobulins, Membrane Glycoproteins, Antigens, CD, Interleukin-10, Gene Expression Profiling, Bystander Effect, Signal Transduction, Cell Differentiation, Gene Expression Regulation, Cell Lineage, Immunity, Innate, Adaptive Immunity, Immune Evasion, Single-Cell Analysis, Primary Cell Culture, CD83 Antigen |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 08 Feb 2019 11:30 |
| Last Modified: | 27 Dec 2023 17:55 |
| DOI: | 10.1038/s41467-018-07329-0 |
| Open Access URL: | http://10.0.4.14/s41467-018-07329-0 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3032518 |
Dimensions
Dimensions
