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- W4313373536 abstract "Abstract Intracellular pathogens have evolved strategies to subvert the host immune response and establish infection leading to disease. For example, Mycobacterium tuberculosis (MTB) has been recently reported to effectively counteract immunological and anti-tubercular challenges by activating resistance mechanisms that enable the pathogen to attain an immune tolerant state. A systems scale approach using dual RNA Sequencing revealed key transcriptional factors that enabled researchers to discover a drug combination that delivers more effective killing of MTB. On the basis of our preliminary findings we hypothesize that similar to MTB, Salmonella spp. have evolved to escape host macrophage responses by down-regulating the expression of flagellin, a potent activator of the NLRC4 inflammasome, by taking advantage of a natural host negative feedback mechanism that allows the pathogen to reside intracellularly within macrophages. However, how Salmonella and host transcriptional networks rewire over the course of infection to permit development of an immune-evasive phenotype in the pathogen remains unknown. Using dual RNA-Seq and regulatory network analysis, we propose to simultaneously identify the molecular changes that occur in both the host and the pathogen during infection. We aim to conduct a temporal study to find transcriptional changes at different time points post infection that lead to development of a permissive host environment and allow Salmonella to undergo immune escape within macrophages. Our study will help identify the key regulators that shape host-pathogen crosstalk over the course of Salmonella infection with potentially important implications for bacterial pathogenesis and immunity." @default.
- W4313373536 created "2023-01-06" @default.
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- W4313373536 date "2020-05-01" @default.
- W4313373536 modified "2023-09-27" @default.
- W4313373536 title "Dual RNA-seq as an effective tool to simultaneously identify transcriptional changes in host macrophages and invading intracellular pathogens" @default.
- W4313373536 doi "https://doi.org/10.4049/jimmunol.204.supp.227.27" @default.
- W4313373536 hasPublicationYear "2020" @default.
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