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

Michael F Goldberg, Elizabeth K. Roeske, Lauren N. Ward, Thomas Pengo, Dileepan T, Dmitri I. Kotov, Marc Jenkins

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1090-1102.e7
JournalImmunity
Volume49
Issue number6
DOIs
StatePublished - Dec 18 2018

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Th1 Cells
Salmonella enterica
Granuloma
Salmonella
Macrophages
Ligands
T-Lymphocytes
Bacteria
Nitric Oxide Synthase
Chemokine CXCL9
CXCR3 Receptors
Infection
Chemokine CXCL10
Poisons
Phagocytes
Chemokines
Innate Immunity
Interferons
Epitopes
Immunity

Keywords

  • CXCR3
  • Th1
  • granuloma
  • phagosomal pathogen

Cite this

Salmonella Persist in Activated Macrophages in T Cell-Sparse Granulomas but Are Contained by Surrounding CXCR3 Ligand-Positioned Th1 Cells. / Goldberg, Michael F; Roeske, Elizabeth K.; Ward, Lauren N.; Pengo, Thomas; T, Dileepan; Kotov, Dmitri I.; Jenkins, Marc.

In: Immunity, Vol. 49, No. 6, 18.12.2018, p. 1090-1102.e7.

Research output: Contribution to journalArticle

Goldberg, Michael F ; Roeske, Elizabeth K. ; Ward, Lauren N. ; Pengo, Thomas ; T, Dileepan ; Kotov, Dmitri I. ; Jenkins, Marc. / Salmonella Persist in Activated Macrophages in T Cell-Sparse Granulomas but Are Contained by Surrounding CXCR3 Ligand-Positioned Th1 Cells. In: Immunity. 2018 ; Vol. 49, No. 6. pp. 1090-1102.e7.
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AB - 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.

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