Trained immunity using probiotics and inactivated pathogens enhances resistance to Salmonella enterica serovar Typhimurium infection by activating the cGAS-STING signal pathway in mice and chickens.

INTRODUCTION: Concerns about antibiotic resistance have prompted interest in alternative strategies for enhancing disease resistance, particularly in livestock and poultry production. OBJECTIVES: This study explored the role of trained immunity in enhancing resistance to Salmonella enterica serovar Typhimurium (S. Typhimurium) infection in mice and chickens. METHODS: We investigated the effects of probiotics and inactivated pathogenic bacterial strains on host immunity in Toll-like receptor 2-deficient mice (TLR2(-)/(-)) to assess whether these effects were related to bacterial outer membrane components such as peptidoglycan (PNG), lipoarabinomannan (LAM) and lipoteichoic acid (LTA). Bacterial genomes were evaluated for their ability to enhance the host immune system. Macrophage-depletion models were used to identify the key immune cells involved in trained immunity, with a focus on the cGAS-STING pathway. RESULTS: Probiotics and inactivated pathogenic strains enhanced host immunity and protected against S. Typhimurium infection. As demonstrated in the TLR2-deficient mice, the effects were not dependent on bacterial outer membrane components. Instead, bacterial genomes played a significant role in activating trained immunity. Macrophages were identified as the primary cells that mediated the response with the cGAS-STING pathway playing a crucial role. The results observed using the mouse models led to investigating the potential application of trained immunity in poultry. CONCLUSION: Trained immunity activated by probiotics and inactivated bacterial pathogens enhanced resistance against S. Typhimurium infection via macrophage activation and involved the cGAS-STING pathway. These findings highlight the potential of trained immunity as an alternative strategy for disease prevention in both livestock and poultry.