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 (STm) infection within the mesenteric lymph nodes (MLN), the main lymphoid tissue of STm persistence. Combining spatial transcriptomics and experimental manipulations, we found that macrophages responding to STm 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.