A non-classical monocyte-derived macrophage subset provides a splenic replication niche for intracellular Salmonella

Dotan Hoffman, Yaara Tevet, Sébastien Trzebanski, Gili Rosenberg, Leia Vainman, Aryeh Solomon, Shelly Hen-Avivi, Noa Bossel Ben-Moshe, Roi Avraham

Research output: Contribution to journalArticlepeer-review

Abstract

Interactions between intracellular bacteria and mononuclear phagocytes give rise to diverse cellular phenotypes that may determine the outcome of infection. Recent advances in single-cell RNA sequencing (scRNA-seq) have identified multiple subsets within the mononuclear population, but implications to their function during infection are limited. Here, we surveyed the mononuclear niche of intracellular Salmonella Typhimurium (S.Tm) during early systemic infection in mice. We described eclipse-like growth kinetics in the spleen, with a first phase of bacterial control mediated by tissue-resident red-pulp macrophages. A second phase involved extensive bacterial replication within a macrophage population characterized by CD9 expression. We demonstrated that CD9+ macrophages induced pathways for detoxificating oxidized lipids, that may be utilized by intracellular S.Tm. We established that CD9+ macrophages originated from non-classical monocytes (NCM), and NCM-depleted mice were more resistant to S.Tm infection. Our study defines macrophage subset-specific host-pathogen interactions that determine early infection dynamics and infection outcome of the entire organism.

Original languageEnglish
Pages (from-to)2712-2723.e6
Number of pages19
JournalImmunity
Volume54
Issue number12
DOIs
StatePublished - 14 Dec 2021

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Immunology and Allergy
  • Immunology

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