Massimiliano BaldassarreDOAA NABEEL ABDALLAH2022-06-062020-10-202022-06-0683363https://drepo.sdl.edu.sa/handle/20.500.14154/67802Macrophages are essential cells of innate immune system; their vital role in recognition and elimination of bacterial pathogen is the fundamental to contain the infection until the adaptive immune response is initiated. Macrophages sense the presence of PathogenAssociated Molecular Patterns (PAMPs) on the pathogen’s surface via pattern recognition receptors (PRRs) including Toll-like receptors (TLRs), scavenger receptors, and NOD-like receptors, which trigger proinflammatory and antimicrobial responses. PRRs-induced signal transduction pathways result in the activation of gene expression encoded inflammatory and innate immune responses including cytokines, chemokines, cell adhesion molecules, and immunoreceptors. Understanding how innate immune cells response to different pathogens is fundamental and can lead to discover new antimicrobial pathways. For example, the study of Salmonella Typhi bacteria led to the discovery of Rab32/BLOC-3, a universal host-defence pathway that protects mammalian species from a wide range of intracellular pathogens. In this study we undertook a detailed, comparative examination of the transcriptional responses of macrophages to Gram-negative Salmonella serovars (S. Typhi, S. Typhimurium) and Grampositive (S. aureus). To investigate how the PAMPs of different pathogens, which act as pathogen ligand to PRRs, induce both common and specific transcriptional profile. Results: we identified the shared and distinct gene expression responses in macrophages. In addition, Salmonellae is a potent macrophage-activating stimulus comparing to S. aureus. TRP53 (P53) is the key player of the cellular responses to the induced DNA damage in Salmonella and S. aureus. Also, Host DNA replication was repressed as a response to the damage in all pathogens related.24enThesis