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

Nat Commun. 2018 Nov 19;9(1):4883. doi: 10.1038/s41467-018-07329-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Bystander Effect*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / microbiology*
  • Cell Differentiation
  • Cell Lineage / immunology*
  • Dendritic Cells / immunology
  • Dendritic Cells / microbiology*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Immune Evasion*
  • Immunity, Innate
  • Immunoglobulins / genetics
  • Immunoglobulins / immunology
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Monocytes / immunology
  • Monocytes / microbiology
  • Primary Cell Culture
  • Salmonella typhimurium / growth & development
  • Salmonella typhimurium / immunology
  • Salmonella typhimurium / pathogenicity*
  • Signal Transduction
  • Single-Cell Analysis
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / immunology

Substances

  • Antigens, CD
  • CD83 antigen
  • IL10 protein, human
  • Immunoglobulins
  • Membrane Glycoproteins
  • Interleukin-10
  • MARCHF1 protein, human
  • Ubiquitin-Protein Ligases