---
_id: '679'
abstract:
- lang: eng
  text: Protective responses against pathogens require a rapid mobilization of resting
    neutrophils and the timely removal of activated ones. Neutrophils are exceptionally
    short-lived leukocytes, yet it remains unclear whether the lifespan of pathogen-engaged
    neutrophils is regulated differently from that in the circulating steady-state
    pool. Here, we have found that under homeostatic conditions, the mRNA-destabilizing
    protein tristetraprolin (TTP) regulates apoptosis and the numbers of activated
    infiltrating murine neutrophils but not neutrophil cellularity. Activated TTP-deficient
    neutrophils exhibited decreased apoptosis and enhanced accumulation at the infection
    site. In the context of myeloid-specific deletion of Ttp, the potentiation of
    neutrophil deployment protected mice against lethal soft tissue infection with
    Streptococcus pyogenes and prevented bacterial dissemination. Neutrophil transcriptome
    analysis revealed that decreased apoptosis of TTP-deficient neutrophils was specifically
    associated with elevated expression of myeloid cell leukemia 1 (Mcl1) but not
    other antiapoptotic B cell leukemia/ lymphoma 2 (Bcl2) family members. Higher
    Mcl1 expression resulted from stabilization of Mcl1 mRNA in the absence of TTP.
    The low apoptosis rate of infiltrating TTP-deficient neutrophils was comparable
    to that of transgenic Mcl1-overexpressing neutrophils. Our study demonstrates
    that posttranscriptional gene regulation by TTP schedules the termination of the
    antimicrobial engagement of neutrophils. The balancing role of TTP comes at the
    cost of an increased risk of bacterial infections.
acknowledgement: This work was supported by grants from the Austrian Science Fund
  (FWF) (P27538-B21, I1621-B22, and SFB 43, to PK); by funding from the European Union
  Seventh Framework Programme Marie Curie Initial Training Networks (FP7-PEOPLE-2012-ITN)
  for the project INBIONET (INfection BIOlogy Training NETwork under grant agreement
  PITN-GA-2012-316682; and by a joint research cluster initiative of the University
  of Vienna and the Medical University of Vienna.
author:
- first_name: Florian
  full_name: Ebner, Florian
  last_name: Ebner
- first_name: Vitaly
  full_name: Sedlyarov, Vitaly
  last_name: Sedlyarov
- first_name: Saren
  full_name: Tasciyan, Saren
  id: 4323B49C-F248-11E8-B48F-1D18A9856A87
  last_name: Tasciyan
  orcid: 0000-0003-1671-393X
- first_name: Masa
  full_name: Ivin, Masa
  last_name: Ivin
- first_name: Franz
  full_name: Kratochvill, Franz
  last_name: Kratochvill
- first_name: Nina
  full_name: Gratz, Nina
  last_name: Gratz
- first_name: Lukas
  full_name: Kenner, Lukas
  last_name: Kenner
- first_name: Andreas
  full_name: Villunger, Andreas
  last_name: Villunger
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
- first_name: Pavel
  full_name: Kovarik, Pavel
  last_name: Kovarik
citation:
  ama: Ebner F, Sedlyarov V, Tasciyan S, et al. The RNA-binding protein tristetraprolin
    schedules apoptosis of pathogen-engaged neutrophils during bacterial infection.
    <i>The Journal of Clinical Investigation</i>. 2017;127(6):2051-2065. doi:<a href="https://doi.org/10.1172/JCI80631">10.1172/JCI80631</a>
  apa: Ebner, F., Sedlyarov, V., Tasciyan, S., Ivin, M., Kratochvill, F., Gratz, N.,
    … Kovarik, P. (2017). The RNA-binding protein tristetraprolin schedules apoptosis
    of pathogen-engaged neutrophils during bacterial infection. <i>The Journal of
    Clinical Investigation</i>. American Society for Clinical Investigation. <a href="https://doi.org/10.1172/JCI80631">https://doi.org/10.1172/JCI80631</a>
  chicago: Ebner, Florian, Vitaly Sedlyarov, Saren Tasciyan, Masa Ivin, Franz Kratochvill,
    Nina Gratz, Lukas Kenner, Andreas Villunger, Michael K Sixt, and Pavel Kovarik.
    “The RNA-Binding Protein Tristetraprolin Schedules Apoptosis of Pathogen-Engaged
    Neutrophils during Bacterial Infection.” <i>The Journal of Clinical Investigation</i>.
    American Society for Clinical Investigation, 2017. <a href="https://doi.org/10.1172/JCI80631">https://doi.org/10.1172/JCI80631</a>.
  ieee: F. Ebner <i>et al.</i>, “The RNA-binding protein tristetraprolin schedules
    apoptosis of pathogen-engaged neutrophils during bacterial infection,” <i>The
    Journal of Clinical Investigation</i>, vol. 127, no. 6. American Society for Clinical
    Investigation, pp. 2051–2065, 2017.
  ista: Ebner F, Sedlyarov V, Tasciyan S, Ivin M, Kratochvill F, Gratz N, Kenner L,
    Villunger A, Sixt MK, Kovarik P. 2017. The RNA-binding protein tristetraprolin
    schedules apoptosis of pathogen-engaged neutrophils during bacterial infection.
    The Journal of Clinical Investigation. 127(6), 2051–2065.
  mla: Ebner, Florian, et al. “The RNA-Binding Protein Tristetraprolin Schedules Apoptosis
    of Pathogen-Engaged Neutrophils during Bacterial Infection.” <i>The Journal of
    Clinical Investigation</i>, vol. 127, no. 6, American Society for Clinical Investigation,
    2017, pp. 2051–65, doi:<a href="https://doi.org/10.1172/JCI80631">10.1172/JCI80631</a>.
  short: F. Ebner, V. Sedlyarov, S. Tasciyan, M. Ivin, F. Kratochvill, N. Gratz, L.
    Kenner, A. Villunger, M.K. Sixt, P. Kovarik, The Journal of Clinical Investigation
    127 (2017) 2051–2065.
date_created: 2018-12-11T11:47:53Z
date_published: 2017-06-01T00:00:00Z
date_updated: 2024-03-25T23:30:12Z
day: '01'
department:
- _id: MiSi
doi: 10.1172/JCI80631
external_id:
  pmid:
  - '28504646'
intvolume: '       127'
issue: '6'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451238/
month: '06'
oa: 1
oa_version: Submitted Version
page: 2051 - 2065
pmid: 1
project:
- _id: 25985A36-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: T00817-B21
  name: The biochemical basis of PAR polarization
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P27201-B22
  name: Revealing the mechanisms underlying drug interactions
publication: The Journal of Clinical Investigation
publication_identifier:
  issn:
  - '00219738'
publication_status: published
publisher: American Society for Clinical Investigation
publist_id: '7038'
quality_controlled: '1'
related_material:
  record:
  - id: '12401'
    relation: dissertation_contains
    status: public
scopus_import: 1
status: public
title: The RNA-binding protein tristetraprolin schedules apoptosis of pathogen-engaged
  neutrophils during bacterial infection
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 127
year: '2017'
...