Single-cell profiling identifies ACE ⁺ granuloma macrophages as a nonpermissive niche for intracellular bacteria during persistent Salmonella infection

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.

Dynamics of macrophage polarization support Salmonella persistence in a whole living organism

“…The complex cellular structure of granuloma is thought to be important for bacterial persistence. Recently, using single-cell transcriptomics, Pham et al identified diverse macrophage populations within Salmonella Typhimurium-induced granulomas ( Pham et al, 2023 ). In the present study, Salmonella persisted within aggregates of tnfa -negative macrophages that remind early granulomas.…”

Dynamics of macrophage polarization supportSalmonellapersistence in a whole living organism

“…The complex cellular structure of granuloma is thought to be important for bacterial persistence. Recently, using single cell transcriptomics, Pham and collaborators identified divers macrophage populations within Salmonella Typhimurium induced granulomas 58 . In this study, Salmonella persisted within aggregates of tnfanegative macrophages that remind early granulomas.…”

Changing Cinnamaldehyde Skeleton Achieves Antibacterial Nanoswitch

“…Most human diseases originate from infections by various microbial bacteria. − The representative drug of the organic class dominates the treatment of bacterial diseases, − but there is antibiotic resistance during treatment process. − Organic drugs such as penicillin, artemisinin, − aspirin, , and valium have been widely used in the treatment of various diseases. The functional group , and conformational relationships of organic drugs play a key role for development of these drugs.…”