TY - JOUR
T1 - Dual RNA sequencing reveals dendritic cell reprogramming in response to typhoidal Salmonella invasion
AU - Aulicino, Anna
AU - Antanaviciute, Agne
AU - Frost, Joe
AU - Geros, Ana Sousa
AU - Mellado, Esther
AU - Attar, Moustafa
AU - Jagielowicz, Marta
AU - Hublitz, Philip
AU - Sinz, Julia
AU - Preciado-Llanes, Lorena
AU - Napolitani, Giorgio
AU - Bowden, Rory
AU - Koohy, Hashem
AU - Drakesmith, Hal
AU - Simmons, Alison
N1 - Funding Information:
This work was supported by a Wellcome Investigator Award 219523/Z/19/Z (A.S.); the University of Oxford’s John Fell Fund (A.A., A.A.A. and A.S.); the UK Medical Research Council (MRC); the Oxford NIHR Biomedical Research Centre; Bristol Myers Squibb (A.A.). We would like to acknowledge Paul Sopp and Craig Waugh in the flow cytometry facility at the MRC WIMM for providing cell sorting services, technical expertise and scientific input. The facility is supported by the MRC HIU; MRC MHU (MC_UU_12009); NIHR Oxford BRC; Kay Kendall Leukaemia Fund (KKL1057), John Fell Fund (131/030 and 101/517), the EPA fund (CF182 and CF170) and by the MRC WIMM Strategic Alliance awards G0902418 and MC_UU_12025. We thank the Oxford Genomics Centre at the Wellcome Centre for Human Genetics (funded by Wellcome Trust grant reference 203141/Z/16/Z) for the generation and initial processing of the sequencing data. We thank Prof. Jay C.D. Hinton for providing the S. Typhimurium strains 4/74 and D37712.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/2/4
Y1 - 2022/2/4
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85124173548&partnerID=8YFLogxK
U2 - 10.1038/s42003-022-03038-z
DO - 10.1038/s42003-022-03038-z
M3 - Article
SN - 2399-3642
VL - 5
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 111
ER -