PMID- 33250899
OWN - NLM
STAT- MEDLINE
DCOM- 20210625
LR  - 20210625
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - Early Cytokine Induction Upon Pseudomonas aeruginosa Infection in Murine 
      Precision Cut Lung Slices Depends on Sensing of Bacterial Viability.
PG  - 598636
LID - 10.3389/fimmu.2020.598636 [doi]
LID - 598636
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.
CI  - Copyright (c) 2020 Kolbe, Yi, Poth, Saunders, Boutin and Dalpke.
FAU - Kolbe, Ulrike
AU  - Kolbe U
AD  - Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg 
      University Hospital, Heidelberg, Germany.
FAU - Yi, Buqing
AU  - Yi B
AD  - Institute of Medical Microbiology and Hygiene, Technische Universitat Dresden, 
      Dresden, Germany.
FAU - Poth, Tanja
AU  - Poth T
AD  - CMCP-Center for Model System and Comparative Pathology, Institute of Pathology, 
      Heidelberg University Hospital, Heidelberg, Germany.
FAU - Saunders, Amy
AU  - Saunders A
AD  - Division of Infection, Immunity and Respiratory Medicine, School of Biological 
      Science, Faculty of Biology, Medicine and Health, Lydia Becker Institute of 
      Immunology and Inflammation, University of Manchester, Manchester Academic Health 
      Science Centre, Manchester, United Kingdom.
FAU - Boutin, Sebastien
AU  - Boutin S
AD  - Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg 
      University Hospital, Heidelberg, Germany.
AD  - Translational Lung Research Center Heidelberg (TLRC), German Center for Lung 
      Research (DZL), University of Heidelberg, Heidelberg, Germany.
FAU - Dalpke, Alexander H
AU  - Dalpke AH
AD  - Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg 
      University Hospital, Heidelberg, Germany.
AD  - Institute of Medical Microbiology and Hygiene, Technische Universitat Dresden, 
      Dresden, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201030
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Cytokines)
RN  - 0 (Type III Secretion Systems)
RN  - 12777-81-0 (Flagellin)
SB  - IM
MH  - Animals
MH  - Biopsy
MH  - Computational Biology/methods
MH  - Cytokines/*metabolism
MH  - Disease Models, Animal
MH  - Flagellin/metabolism
MH  - Gene Expression Profiling
MH  - *Host-Pathogen Interactions/genetics/immunology
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Knockout
MH  - Microbial Viability
MH  - Pneumonia, Bacterial/genetics/immunology/*metabolism/*microbiology
MH  - Pseudomonas Infections/genetics/immunology/*metabolism/*microbiology
MH  - Pseudomonas aeruginosa/*physiology
MH  - Transcriptome
MH  - Type III Secretion Systems/metabolism
PMC - PMC7673395
OTO - NOTNLM
OT  - Pseudomonas aeruginosa
OT  - infection and immunity
OT  - innate immunity
OT  - live/dead discrimination
OT  - precision cut lung slice
EDAT- 2020/12/01 06:00
MHDA- 2021/06/29 06:00
PMCR- 2020/01/01
CRDT- 2020/11/30 05:53
PHST- 2020/08/25 00:00 [received]
PHST- 2020/10/07 00:00 [accepted]
PHST- 2020/11/30 05:53 [entrez]
PHST- 2020/12/01 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.598636 [doi]
PST - epublish
SO  - Front Immunol. 2020 Oct 30;11:598636. doi: 10.3389/fimmu.2020.598636. eCollection 
      2020.