Salmonella Persistence and Host Immunity Are Dictated by the Anatomical Microenvironment

Infect Immun. 2020 Jul 21;88(8):e00026-20. doi: 10.1128/IAI.00026-20. Print 2020 Jul 21.


The intracellular bacterial pathogen Salmonella is able to evade the immune system and persist within the host. In some cases, these persistent infections are asymptomatic for long periods and represent a significant public health hazard because the hosts are potential chronic carriers, yet the mechanisms that control persistence are incompletely understood. Using a mouse model of chronic typhoid fever combined with major histocompatibility complex (MHC) class II tetramers to interrogate endogenous, Salmonella-specific CD4+ helper T cells, we show that certain host microenvironments may favorably contribute to a pathogen's ability to persist in vivo We demonstrate that the environment in the hepatobiliary system may contribute to the persistence of Salmonella enterica subsp. enterica serovar Typhimurium through liver-resident immunoregulatory CD4+ helper T cells, alternatively activated macrophages, and impaired bactericidal activity. This contrasts with lymphoid organs, such as the spleen and mesenteric lymph nodes, where these same cells appear to have a greater capacity for bacterial killing, which may contribute to control of bacteria in these organs. We also found that, following an extended period of infection of more than 2 years, the liver appeared to be the only site that harbored Salmonella bacteria. This work establishes a potential role for nonlymphoid organ immunity in regulating chronic bacterial infections and provides further evidence for the hepatobiliary system as the site of chronic Salmonella infection.

Keywords: CD4 T cell; Salmonella; immune regulation; liver immunology; macrophages.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chronic Disease
  • Coculture Techniques
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / immunology
  • Gallbladder / immunology
  • Gallbladder / microbiology
  • Gene Expression Regulation / immunology
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology*
  • Immunity, Innate
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Liver / immunology*
  • Liver / microbiology
  • Lymph Nodes / immunology
  • Lymph Nodes / microbiology
  • Macrophage Activation
  • Mice
  • Mice, Inbred C57BL
  • Organ Specificity
  • RAW 264.7 Cells
  • Salmonella Infections, Animal / genetics
  • Salmonella Infections, Animal / immunology*
  • Salmonella Infections, Animal / microbiology
  • Salmonella Infections, Animal / pathology
  • Salmonella typhimurium / growth & development
  • Salmonella typhimurium / immunology*
  • Salmonella typhimurium / pathogenicity
  • Single-Cell Analysis
  • Spleen / immunology
  • Spleen / microbiology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / microbiology


  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • IL10 protein, mouse
  • Interleukin-10
  • Interferon-gamma