Invasive Salmonella exploits divergent immune evasion strategies in infected and bystander dendritic cell subsets.
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
Author Information
Anna Aulicino: MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Kevin C Rue-Albrecht: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Headington, Oxford, OX3 7FY, UK. ORCID
Lorena Preciado-Llanes: MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Giorgio Napolitani: MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Neil Ashley: MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford and BRC Blood Theme, NIHR Oxford Biomedical Centre, Oxford, OX3 9DS, UK.
Adam Cribbs: MRC WIMM Centre for Computational Biology, MRC Weatherall Institute of Molecular medicine, University of Oxford, Oxford, OX3 9DS, UK.
Jana Koth: MRC Human Immunology Unit and Wolfson Imaging Centre, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
B Christoffer Lagerholm: MRC Human Immunology Unit and Wolfson Imaging Centre, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Tim Ambrose: MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Melita A Gordon: Institute of Infection and Global Health, University of Liverpool, 8 W Derby St, Liverpool, L7 3EA, UK.
David Sims: MRC WIMM Centre for Computational Biology, MRC Weatherall Institute of Molecular medicine, University of Oxford, Oxford, OX3 9DS, UK.
Alison Simmons: MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. alison.simmons@ndm.ox.ac.uk. ORCID
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.
