Salmonella Persist in Activated Macrophages in T Cell-Sparse Granulomas but Are Contained by Surrounding CXCR3 Ligand-Positioned Th1 Cells

Immunity. 2018 Dec 18;49(6):1090-1102.e7. doi: 10.1016/j.immuni.2018.10.009. Epub 2018 Dec 11.


Salmonella enterica (Se) bacteria cause persistent intracellular infections while stimulating a robust interferon-γ-producing CD4+ T (Th1) cell response. We addressed this paradox of concomitant infection and immunity by tracking fluorescent Se organisms in mice. Se bacteria persisted in nitric oxide synthase (iNOS)-producing resident and recruited macrophages while inducing genes related to protection from nitric oxide. Se-infected cells occupied iNOS+ splenic granulomas that excluded T cells but were surrounded by mononuclear phagocytes producing the chemokines CXCL9 and CXCL10, and Se epitope-specific Th1 cells expressing CXCR3, the receptor for these chemokines. Blockade of CXCR3 inhibited Th1 occupancy of CXCL9/10-dense regions, reduced activation of the Th1 cells, and led to increased Se growth. Thus, intracellular Se bacteria survive in their hosts by counteracting toxic products of the innate immune response and by residing in T cell-sparse granulomas, away from abundant Th1 cells positioned via CXCR3 in a bordering region that act to limit infection.

Keywords: CXCR3; Th1; granuloma; phagosomal pathogen.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / microbiology
  • Chemokine CXCL10 / immunology
  • Chemokine CXCL10 / metabolism
  • Chemokine CXCL9 / immunology
  • Chemokine CXCL9 / metabolism
  • Granuloma / immunology*
  • Granuloma / metabolism
  • Granuloma / microbiology
  • Host-Pathogen Interactions / immunology
  • Ligands
  • Macrophage Activation / immunology
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, CXCR3 / immunology*
  • Receptors, CXCR3 / metabolism
  • Salmonella Infections / immunology*
  • Salmonella Infections / metabolism
  • Salmonella Infections / microbiology
  • Salmonella enterica / immunology*
  • Salmonella enterica / physiology
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th1 Cells / microbiology


  • Chemokine CXCL10
  • Chemokine CXCL9
  • Ligands
  • Receptors, CXCR3