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• W4313706739 abstract "Macrophages mediate key antimicrobial responses against intracellular bacterial pathogens, such as Salmonella enterica . Yet, they can also act as a permissive niche for these pathogens to persist in infected tissues within granulomas, which are immunological structures composed of macrophages and other immune cells. We apply single-cell transcriptomics to investigate macrophage functional diversity during persistent S. enterica serovar Typhimurium ( S Tm) infection in mice. We identify determinants of macrophage heterogeneity in infected spleens and describe populations of distinct phenotypes, functional programming, and spatial localization. Using an S Tm mutant with impaired ability to polarize macrophage phenotypes, we find that angiotensin-converting enzyme (ACE) defines a granuloma macrophage population that is nonpermissive for intracellular bacteria, and their abundance anticorrelates with tissue bacterial burden. Disruption of pathogen control by neutralizing TNF is linked to preferential depletion of ACE + macrophages in infected tissues. Thus, ACE + macrophages have limited capacity to serve as cellular niche for intracellular bacteria to establish persistent infection." @default.
• W4313706739 created "2023-01-08" @default.
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• W4313706739 date "2023-01-06" @default.
• W4313706739 modified "2023-09-29" @default.
• W4313706739 title "Single-cell profiling identifies ACE ⁺ granuloma macrophages as a nonpermissive niche for intracellular bacteria during persistent <i>Salmonella</i> infection" @default.
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• W4313706739 doi "https://doi.org/10.1126/sciadv.add4333" @default.
• W4313706739 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36608122" @default.
• W4313706739 hasPublicationYear "2023" @default.
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