Eosinophils Enhance Granuloma-Mediated Control of Persistent Salmonella Infection

Salmonella enterica can persist asymptomatically within tissues for extended periods. This remarkable feat is achieved through intricate host-pathogen interactions in immune cell aggregates called granulomas, wherein Salmonella find favorable cellular niches to exploit while the host limits its expansion and tissue dissemination. Here, using a mouse model of persistent Salmonella infection, we identify a host-protective role of eosinophils in control of Salmonella Typhimurium ( S Tm) infection within the mesenteric lymph nodes (MLN), the main lymphoid tissue of S Tm persistence. Combining spatial transcriptomics and experimental manipulations, we found that macrophages responding to S Tm infection recruited eosinophils in a C-C motif chemokine ligand 11 (CCL11)-dependent manner and enhanced their activation. Eosinophil deficiencies increased Salmonella burdens, which was associated with altered granuloma size and impaired type-1 immunity in the MLN. Thus, eosinophils play a vital role in restraining Salmonella exploitation of granuloma macrophages at a key site of bacterial persistence.