Eosinophils enhance granuloma-mediated control of persistent Salmonella infection in mice

Salmonella enterica can persist asymptomatically within tissues for extended periods. This is achieved through intricate host-pathogen interactions in immune cell aggregates called granulomas, wherein Salmonella establish favourable 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 for eosinophils in the control of Salmonella Typhimurium (STm) infection within the mesenteric lymph nodes, the main lymphoid tissue of STm persistence. Combining spatial transcriptomics and experimental manipulations, we found that monocytes and macrophages responding to STm infection recruited eosinophils in a C-C motif chemokine ligand 11 (CCL11)-dependent manner and enhanced their activation. The protein major basic protein, primarily expressed by eosinophils, was associated with altered macrophage polarization and bacterial control. Thus, eosinophils play a vital role in restraining Salmonella exploitation of granuloma macrophages at a key site of bacterial persistence.