Proteomics profiling reveals regulation of immune response to Salmonella Typhimurium infection in mice

Abstract Regulation of the immune response to Salmonella typhimurium ( S . Typhimurium) infection is a complex process, influenced by genetic and environmental factors. Different inbred mouse strains show distinct levels of resistance to S . Typhimurium infection, ranging from susceptible (e.g., C57BL/6J) to resistant (e.g., DBA/2J) strains. However, the underlying molecular mechanisms contributing to the host response remain elusive. In this study, we present a comprehensive proteomics profiling of the spleen tissue from C57BL/6J and DBA/2J strains with different doses of S . Typhimurium infection by tandem tag mass coupled with two-dimensional liquid chromatography-tandem mass spectrometry. We identified and quantified 3,986 proteins, resulting in 475 differentially expressed proteins between C57BL/6J and DBA/2J strains. Functional enrichment analysis revealed that the mechanisms of innate immune responses to S . Typhimurium infection are associated with several signaling pathways, including the interferon signaling pathway. Our proteomic data also discovered a plausible gene in a genomic region that control different levels of resistance to S . Typhimurium infection. We further revealed the roles of macrophage cells and pro-inflammatory cytokines in the mechanisms under the natural resistance to S . Typhimurium. In summary, our results provide new insights into the genetic regulation of the immune response to S . Typhimurium infection in mice. Author Summary Salmonella infection (salmonellosis) is a common zoonotic disease that mainly propagates through contaminated food and drink. Various mouse strains display prominent disparities in responses to Salmonella invasion. Elucidating the heterogeneous immune reactions between different mouse strains can shed light on the fundamental molecular mechanisms of the innate immune system. Here, we employed a combination of proteomics and systems biology approaches to provide an unprecedented panorama of the inextricably interlaced immune signaling pathways in response to Salmonella infection in mice. Our results revealed the dynamics of cell signaling molecules elicited by inflammation and established new connections among them. We also identified a new candidate gene involved in the combat with pathogens. Our proteomic data and results contribute to understanding the intricate interactions of immune responses to Salmonella infection from molecular to systemic levels.