A host innate immune circuit licenses downregulation of Salmonella flagellin expression inside macrophages
| Autor: | Ajay Suresh Akhade, Shaikh M Atif, Bhavna S Lakshmi, Neha Dikshit, Ayub Qadri, Naeha Subramanian |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 204:226.12-226.12 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.204.supp.226.12 |
| Popis: | While the effect of bacterial molecules on host immune system is well studied, how host factors affect expression of bacterial molecules is not understood in great detail. Inflammasomes are instrumental in detection and clearance of bacterial pathogens, but little is known about whether there is an active cross-talk between the host sensing mechanism and the expression of stimulatory ligands by the pathogen. We used Salmonella-macrophage infection model to assess the impact of inflammasome activation on the expression of flagellin as a candidate Salmonella protein. We discovered that early during infection, host lysophospholipids released upon rapid NLRC4-mediated pyroptosis of macrophages increase flagellin expression by extracellular bacteria which leads to even greater pyroptosis when these bacteria infect healthy macrophages, thus facilitating NLRC4-mediated detection and clearance of Salmonella. A TLR-dependent host response, however, later inhibits expression of NLRC4 and the lysophospholipid biosynthetic enzyme iPLA2, causing a decline in intracellular lysophospholipids pool that permits downregulation of flagellin by intracellular Salmonella. Our findings reveal a novel mode of host-pathogen cross-talk wherein expression of a bacterium-derived inflammasome ligand is temporally controlled by the very process of inflammasome activation, and identify a host mechanism that controls switching of Salmonella to a flagellin-low phenotype inside macrophages with important implications for bacterial pathogenesis and immunity. Future investigations will utilize dual RNA-Seq studies to understand how Salmonella gene expression networks rewire to adapt to different host intracellular microenvironments. |
| Databáze: | OpenAIRE |
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