Early Cytokine Induction Upon Pseudomonas aeruginosa Infection in Murine Precision Cut Lung Slices Depends on Sensing of Bacterial Viability

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Microbes, Pathogens and Immunity

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https://doi.org/10.3389/fimmu.2020.598636
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Available under license: CC BY: Creative Commons Attribution 4.0 International License

Keywords

Animals, Biopsy, Computational Biology/methods, Cytokines/metabolism, Disease Models, Animal, Flagellin/metabolism, Gene Expression Profiling, Host-Pathogen Interactions/genetics, Immunohistochemistry, Mice, Mice, Knockout, Microbial Viability, Pneumonia, Bacterial/genetics, Pseudomonas Infections/genetics, Pseudomonas aeruginosa/physiology, Transcriptome, Type III Secretion Systems/metabolism

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Early Cytokine Induction Upon Pseudomonas aeruginosa Infection in Murine Precision Cut Lung Slices Depends on Sensing of Bacterial Viability. / Kolbe, Ulrike; Yi, Buqing; Poth, Tanja et al.
In: Frontiers in Immunology, Vol. 11, 598636, 30.10.2020.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Bibtex

@article{ec91663565c447f19dd8a96a900e55b4,

title = "Early Cytokine Induction Upon Pseudomonas aeruginosa Infection in Murine Precision Cut Lung Slices Depends on Sensing of Bacterial Viability",

abstract = "Breathing allows a multitude of airborne microbes and microbial compounds to access the lung. Constant exposure of the pulmonary microenvironment to immunogenic particles illustrates the need for proper control mechanisms ensuring the differentiation between threatening and harmless encounters. Discrimination between live and dead bacteria has been suggested to be such a mechanism. In this study, we performed infection studies of murine precision cut lung slices (PCLS) with live or heat-killed P. aeruginosa, in order to investigate the role of viability for induction of an innate immune response. We demonstrate that PCLS induce a robust transcriptomic rewiring upon infection with live but not heat-killed P. aeruginosa. Using mutants of the P. aeruginosa clinical isolate CHA, we show that the viability status of P. aeruginosa is assessed in PCLS by TLR5-independent sensing of flagellin and recognition of the type three secretion system. We further demonstrate that enhanced cytokine expression towards live P. aeruginosa is mediated by uptake of viable but not heat-killed bacteria. Finally, by using a combined approach of receptor blockage and genetically modified PCLS we report a redundant involvement of MARCO and CD200R1 in the uptake of live P. aeruginosa in PCLS. Altogether, our results show that PCLS adapt the extent of cytokine expression to the viability status of P. aeruginosa by specifically internalizing live bacteria.",

keywords = "Animals, Biopsy, Computational Biology/methods, Cytokines/metabolism, Disease Models, Animal, Flagellin/metabolism, Gene Expression Profiling, Host-Pathogen Interactions/genetics, Immunohistochemistry, Mice, Mice, Knockout, Microbial Viability, Pneumonia, Bacterial/genetics, Pseudomonas Infections/genetics, Pseudomonas aeruginosa/physiology, Transcriptome, Type III Secretion Systems/metabolism",

author = "Ulrike Kolbe and Buqing Yi and Tanja Poth and Amy Saunders and S{\'e}bastien Boutin and Dalpke, {Alexander H}",

year = "2020",

month = oct,

day = "30",

doi = "10.3389/fimmu.2020.598636",

language = "English",

volume = "11",

journal = "Frontiers in Immunology",

issn = "1664-3224",

publisher = "Frontiers Media S.A.",

}

RIS

TY - JOUR

T1 - Early Cytokine Induction Upon Pseudomonas aeruginosa Infection in Murine Precision Cut Lung Slices Depends on Sensing of Bacterial Viability

AU - Kolbe, Ulrike

AU - Yi, Buqing

AU - Poth, Tanja

AU - Saunders, Amy

AU - Boutin, Sébastien

AU - Dalpke, Alexander H

PY - 2020/10/30

Y1 - 2020/10/30

N2 - Breathing allows a multitude of airborne microbes and microbial compounds to access the lung. Constant exposure of the pulmonary microenvironment to immunogenic particles illustrates the need for proper control mechanisms ensuring the differentiation between threatening and harmless encounters. Discrimination between live and dead bacteria has been suggested to be such a mechanism. In this study, we performed infection studies of murine precision cut lung slices (PCLS) with live or heat-killed P. aeruginosa, in order to investigate the role of viability for induction of an innate immune response. We demonstrate that PCLS induce a robust transcriptomic rewiring upon infection with live but not heat-killed P. aeruginosa. Using mutants of the P. aeruginosa clinical isolate CHA, we show that the viability status of P. aeruginosa is assessed in PCLS by TLR5-independent sensing of flagellin and recognition of the type three secretion system. We further demonstrate that enhanced cytokine expression towards live P. aeruginosa is mediated by uptake of viable but not heat-killed bacteria. Finally, by using a combined approach of receptor blockage and genetically modified PCLS we report a redundant involvement of MARCO and CD200R1 in the uptake of live P. aeruginosa in PCLS. Altogether, our results show that PCLS adapt the extent of cytokine expression to the viability status of P. aeruginosa by specifically internalizing live bacteria.

AB - Breathing allows a multitude of airborne microbes and microbial compounds to access the lung. Constant exposure of the pulmonary microenvironment to immunogenic particles illustrates the need for proper control mechanisms ensuring the differentiation between threatening and harmless encounters. Discrimination between live and dead bacteria has been suggested to be such a mechanism. In this study, we performed infection studies of murine precision cut lung slices (PCLS) with live or heat-killed P. aeruginosa, in order to investigate the role of viability for induction of an innate immune response. We demonstrate that PCLS induce a robust transcriptomic rewiring upon infection with live but not heat-killed P. aeruginosa. Using mutants of the P. aeruginosa clinical isolate CHA, we show that the viability status of P. aeruginosa is assessed in PCLS by TLR5-independent sensing of flagellin and recognition of the type three secretion system. We further demonstrate that enhanced cytokine expression towards live P. aeruginosa is mediated by uptake of viable but not heat-killed bacteria. Finally, by using a combined approach of receptor blockage and genetically modified PCLS we report a redundant involvement of MARCO and CD200R1 in the uptake of live P. aeruginosa in PCLS. Altogether, our results show that PCLS adapt the extent of cytokine expression to the viability status of P. aeruginosa by specifically internalizing live bacteria.

KW - Animals

KW - Biopsy

KW - Computational Biology/methods

KW - Cytokines/metabolism

KW - Disease Models, Animal

KW - Flagellin/metabolism

KW - Gene Expression Profiling

KW - Host-Pathogen Interactions/genetics

KW - Immunohistochemistry

KW - Mice

KW - Mice, Knockout

KW - Microbial Viability

KW - Pneumonia, Bacterial/genetics

KW - Pseudomonas Infections/genetics

KW - Pseudomonas aeruginosa/physiology

KW - Transcriptome

KW - Type III Secretion Systems/metabolism

U2 - 10.3389/fimmu.2020.598636

DO - 10.3389/fimmu.2020.598636

M3 - Journal article

C2 - 33250899

VL - 11

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 598636

ER -

Research

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