PMID- 35121793 OWN - NLM STAT- MEDLINE DCOM- 20220324 LR - 20221023 IS - 2399-3642 (Electronic) IS - 2399-3642 (Linking) VI - 5 IP - 1 DP - 2022 Feb 4 TI - Dual RNA sequencing reveals dendritic cell reprogramming in response to typhoidal Salmonella invasion. PG - 111 LID - 10.1038/s42003-022-03038-z [doi] LID - 111 AB - Salmonella enterica represent a major disease burden worldwide. S. enterica serovar Typhi (S. Typhi) is responsible for potentially life-threatening Typhoid fever affecting 10.9 million people annually. While non-typhoidal Salmonella (NTS) serovars usually trigger self-limiting diarrhoea, invasive NTS bacteraemia is a growing public health challenge. Dendritic cells (DCs) are key professional antigen presenting cells of the human immune system. The ability of pathogenic bacteria to subvert DC functions and prevent T cell recognition contributes to their survival and dissemination within the host. Here, we adapted dual RNA-sequencing to define how different Salmonella pathovariants remodel their gene expression in tandem with that of infected DCs. We find DCs harness iron handling pathways to defend against invading Salmonellas, which S. Typhi is able to circumvent by mounting a robust response to nitrosative stress. In parallel, we uncover the alternative strategies invasive NTS employ to impair DC functions. CI - (c) 2022. The Author(s). FAU - Aulicino, Anna AU - Aulicino A AUID- ORCID: 0000-0002-3407-2796 AD - MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. AD - Translational Gastroenterology Unit, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK. FAU - Antanaviciute, Agne AU - Antanaviciute A AD - MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. AD - Translational Gastroenterology Unit, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK. AD - MRC WIMM Centre for Computational Biology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. FAU - Frost, Joe AU - Frost J AD - MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. FAU - Sousa Geros, Ana AU - Sousa Geros A AUID- ORCID: 0000-0002-6262-755X AD - MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. AD - Translational Gastroenterology Unit, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK. FAU - Mellado, Esther AU - Mellado E AD - Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7BN, UK. FAU - Attar, Moustafa AU - Attar M AD - Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7BN, UK. AD - Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7FY, UK. FAU - Jagielowicz, Marta AU - Jagielowicz M AD - MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. AD - Translational Gastroenterology Unit, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK. FAU - Hublitz, Philip AU - Hublitz P AUID- ORCID: 0000-0001-8810-3247 AD - MRC Weatherall Institute of Molecular Medicine, Genome Engineering Facility, University of Oxford, Oxford, OX3 9DS, UK. FAU - Sinz, Julia AU - Sinz J AD - MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. AD - Translational Gastroenterology Unit, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK. FAU - Preciado-Llanes, Lorena AU - Preciado-Llanes L AUID- ORCID: 0000-0001-5120-3578 AD - MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. AD - Translational Gastroenterology Unit, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK. FAU - Napolitani, Giorgio AU - Napolitani G AD - MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. FAU - Bowden, Rory AU - Bowden R AD - Wellcome Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7BN, UK. FAU - Koohy, Hashem AU - Koohy H AUID- ORCID: 0000-0002-3640-7043 AD - MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. AD - MRC WIMM Centre for Computational Biology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. FAU - Drakesmith, Hal AU - Drakesmith H AD - MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. FAU - Simmons, Alison AU - Simmons A AUID- ORCID: 0000-0003-3454-0710 AD - MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK. alison.simmons@ndm.ox.ac.uk. AD - Translational Gastroenterology Unit, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK. alison.simmons@ndm.ox.ac.uk. LA - eng GR - MC_UU_00008/7/MRC_/Medical Research Council/United Kingdom GR - MC_UU_12025/MRC_/Medical Research Council/United Kingdom GR - MC_UU_00008/10/MRC_/Medical Research Council/United Kingdom GR - MR/S036377/1/MRC_/Medical Research Council/United Kingdom GR - 219523/Z/19/Z/Wellcome/ GR - MC_UU_12009/MRC_/Medical Research Council/United Kingdom GR - G0902418/MRC_/Medical Research Council/United Kingdom GR - 203141/Z/16/Z/WT_/Wellcome Trust/United Kingdom GR - MC_UU_12010/7/MRC_/Medical Research Council/United Kingdom GR - MC_PC_MR/S025952/1/MRC_/Medical Research Council/United Kingdom GR - WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220204 PL - England TA - Commun Biol JT - Communications biology JID - 101719179 SB - IM MH - Cellular Reprogramming/*physiology MH - Dendritic Cells/immunology/*metabolism MH - Gene Expression Regulation/drug effects MH - Humans MH - Mutation MH - Salmonella enterica/*classification PMC - PMC8816929 COIS- The authors declare no competing interests. EDAT- 2022/02/06 06:00 MHDA- 2022/03/25 06:00 PMCR- 2022/02/04 CRDT- 2022/02/05 05:49 PHST- 2021/03/31 00:00 [received] PHST- 2021/12/15 00:00 [accepted] PHST- 2022/02/05 05:49 [entrez] PHST- 2022/02/06 06:00 [pubmed] PHST- 2022/03/25 06:00 [medline] PHST- 2022/02/04 00:00 [pmc-release] AID - 10.1038/s42003-022-03038-z [pii] AID - 3038 [pii] AID - 10.1038/s42003-022-03038-z [doi] PST - epublish SO - Commun Biol. 2022 Feb 4;5(1):111. doi: 10.1038/s42003-022-03038-z.