Multi-omics approaches reveal inflammatory response and intestinal damage mediated by sRNA SaaS during Salmonella invasion in mice

Abstract

Salmonella Enteritidis is a foodborne enteric pathogen that infects humans and animals, and bacterial small RNAs (sRNAs) have been found to play critical roles in the virulence of Salmonella. However, the specific mechanism by which sRNAs contribute to the host–pathogen interaction in the intestine remains unclear. In this study, a combination of transcriptomic and proteomic analysis was used to investigate the effect of a particular sRNA known as Salmonella adhesive-associated sRNA (SaaS) on the intestinal damage induced by Salmonella. The results revealed that SaaS sRNA could suppress the host's inflammatory response through various gene sets, mainly including tumor necrosis factor (TNF)-α signaling via NF-κB, IL-6 JAK-STAT3 signaling, and interferon gamma responses. This suppressive effect was further confirmed by ELISA analysis, which showed the lowest levels of TNF-α, IL-6, and interferon gamma (IFN-γ). Meanwhile, the work has identified several crucial factors, peptidoglycan recognition protein short, transferrin receptor protein 1, and corticosteroid 11-beta-dehydrogenase isozyme 2, that are specifically targeted by SaaS to regulate inflammatory response, neutrophils activity, and diseases. Furthermore, combining hematologic analysis and correlation analysis, this study demonstrated that SaaS led to a decrease in the percentage of neutrophils and revealed a strong correlation between the three crucial factors and various markers of inflammation and intestinal barrier function. These findings provide a comprehensive understanding of how SaaS sRNA modulates Salmonella invasion in the animal intestine and further present a strategy on controlling foodborne Salmonella based on the new targets, sRNAs.