Single-cell RNA-seq ties macrophage polarization to growth rate of intracellular Salmonella

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Title: Single-cell RNA-seq ties macrophage polarization to growth rate of intracellular Salmonella
Author(s): Saliba, A-E
Li, L
Westermann, AJ
Appenzeller, S
Stapels, DAC
Schulte, LN
Helaine, S
Vogel, J
Item Type: Journal Article
Abstract: Intracellular bacterial pathogens can exhibit large heterogeneity in growth rate inside host cells, with major consequences for the infection outcome. If and how the host responds to this heterogeneity remains poorly understood. Here, we combined a fluorescent reporter of bacterial cell division with single-cell RNA-sequencing analysis to study the macrophage response to different intracellular states of the model pathogen Salmonella enterica serovar Typhimurium. The transcriptomes of individual infected macrophages revealed a spectrum of functional host response states to growing and non-growing bacteria. Intriguingly, macrophages harbouring non-growing Salmonella display hallmarks of the proinflammatory M1 polarization state and differ little from bystander cells, suggesting that non-growing bacteria evade recognition by intracellular immune receptors. By contrast, macrophages containing growing bacteria have turned into an anti-inflammatory, M2-like state, as if fast-growing intracellular Salmonella overcome host defence by reprogramming macrophage polarization. Additionally, our clustering approach reveals intermediate host functional states between these extremes. Altogether, our data suggest that gene expression variability in infected host cells shapes different cellular environments, some of which may favour a growth arrest of Salmonella facilitating immune evasion and the establishment of a long-term niche, while others allow Salmonella to escape intracellular antimicrobial activity and proliferate.
Publication Date: 14-Nov-2016
Date of Acceptance: 16-Sep-2016
URI: http://hdl.handle.net/10044/1/65514
DOI: https://dx.doi.org/10.1038/nmicrobiol.2016.206
ISSN: 2058-5276
Publisher: Nature Research
Journal / Book Title: Nature Microbiology
Volume: 2
Issue: 2
Sponsor/Funder: Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: MR/M009629/1
MR/M009629/1
Copyright Statement: © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Keywords: Science & Technology
Life Sciences & Biomedicine
Microbiology
BACTERIAL-INFECTIONS
EXPRESSION ANALYSIS
IMMUNE-RESPONSES
HOST RESPONSES
PATHOGEN
HETEROGENEITY
GENE
SMART-SEQ2
RECEPTORS
DIVERSITY
Animals
Biological Variation, Population
Cell Differentiation
Cells, Cultured
Gene Expression Profiling
Host-Pathogen Interactions
Macrophages
Mice, Inbred C57BL
Salmonella typhimurium
Sequence Analysis, RNA
Single-Cell Analysis
Cells, Cultured
Macrophages
Animals
Mice, Inbred C57BL
Salmonella typhimurium
Gene Expression Profiling
Sequence Analysis, RNA
Cell Differentiation
Host-Pathogen Interactions
Single-Cell Analysis
Biological Variation, Population
Science & Technology
Life Sciences & Biomedicine
Microbiology
BACTERIAL-INFECTIONS
EXPRESSION ANALYSIS
IMMUNE-RESPONSES
HOST RESPONSES
PATHOGEN
HETEROGENEITY
GENE
SMART-SEQ2
RECEPTORS
DIVERSITY
Publication Status: Published
Article Number: ARTN 16206
Appears in Collections:Department of Medicine
Faculty of Medicine



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