Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/11484
Title: Bacterial internalization, localization, and effectors shape the epithelial immune response during Shigella flexneri infection
Authors: Lippmann, J
Gwinner, F
Rey, C
Tamir, U
Law, HKW 
Schwikowski, B
Enninga, J
Issue Date: 2015
Publisher: American Society for Microbiology
Source: Infection and immunity, 2015, v. 83, no. 9, p. 3624-3637 How to cite?
Journal: Infection and immunity 
Abstract: Intracellular pathogens are differentially sensed by the compartmentalized host immune system. Nevertheless, gene expression studies of infected cells commonly average the immune responses, neglecting the precise pathogen localization. To overcome this limitation, we dissected the transcriptional immune response to Shigella flexneri across different infection stages in bulk and single cells. This identified six distinct transcriptional profiles characterizing the dynamic, multilayered host response in both bystander and infected cells. These profiles were regulated by external and internal danger signals, as well as whether bacteria were membrane bound or cytosolic. We found that bacterial internalization triggers a complex, effector-independent response in bystander cells, possibly to compensate for the undermined host gene expression in infected cells caused by bacterial effectors, particularly OspF. Single-cell analysis revealed an important bacterial strategy to subvert host responses in infected cells, demonstrating that OspF disrupts concomitant gene expression of proinflammatory, apoptosis, and stress pathways within cells. This study points to novel mechanisms through which bacterial internalization, localization, and injected effectors orchestrate immune response transcriptional signatures.
URI: http://hdl.handle.net/10397/11484
ISSN: 0019-9567
EISSN: 1098-5522
DOI: 10.1128/IAI.00574-15
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