PMID- 36535641
OWN - NLM
STAT- MEDLINE
DCOM- 20230206
LR  - 20230302
IS  - 2049-632X (Electronic)
IS  - 2049-632X (Linking)
VI  - 81
DP  - 2023 Jan 17
TI  - Role of Hypoxia-inducible factor 1alpha in host defense during pneumococcal 
      pneumonia.
LID - ftac047 [pii]
LID - 10.1093/femspd/ftac047 [doi]
AB  - Hypoxia-inducible factor (HIF)1alpha is a transcription factor involved in cellular 
      metabolism and regulation of immune cell effector functions. Here, we studied the 
      role of HIF1alpha in myeloid cells during pneumonia caused by the major causative 
      pathogen, Streptococcus pneumoniae (Spneu). Mice deficient for HIF1alpha in myeloid 
      cells (LysMcreHif1alphafl/fl) were generated to study the in vitro responsiveness of 
      bone marrow-derived macrophages (BMDMs) and alveolar macrophages (AMs) to the 
      Gram-positive bacterial wall component lipoteichoic acid (LTA) and heat-killed 
      Spneu, and the in vivo host response after infection with Spneu via the airways. 
      Both BMDMs and AMs released more lactate upon stimulation with LTA or Spneu, 
      indicative of enhanced glycolysis; HIF1alpha-deficiency in these cells was associated 
      with diminished lactate release. In BMDMs, HIF1alpha-deficiency resulted in reduced 
      secretion of tumor necrosis factor (TNF)alpha and interleukin (IL)-6 upon activation 
      with Spneu but not LTA, while HIF1alpha-deficient AMs secreted less TNFalpha and IL-6 in 
      response to LTA, and TNFalpha after Spneu stimulation. However, no difference was 
      found in the host response of LysMcreHif1alphafl/fl mice after Spneu infection as 
      compared to controls. Similar in vivo findings were obtained in neutrophil 
      (Mrp8creHif1alphafl/fl) HIF1alpha-deficient mice. These data suggest that myeloid HIF1alpha 
      is dispensable for the host defense during pneumococcal pneumonia.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.
FAU - Pereverzeva, Liza
AU  - Pereverzeva L
AUID- ORCID: 0000-0001-9091-7506
AD  - Center of Experimental & Molecular Medicine, Amsterdam University Medical 
      Centers, Location Academic Medical Center, University of Amsterdam, 1105 AZ 
      Amsterdam, the Netherlands.
AD  - Amsterdam Infection & Immunity Institute, Amsterdam University Medical Centers, 
      Location Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the 
      Netherlands.
FAU - Otto, Natasja A
AU  - Otto NA
AD  - Center of Experimental & Molecular Medicine, Amsterdam University Medical 
      Centers, Location Academic Medical Center, University of Amsterdam, 1105 AZ 
      Amsterdam, the Netherlands.
AD  - Amsterdam Infection & Immunity Institute, Amsterdam University Medical Centers, 
      Location Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the 
      Netherlands.
FAU - Peters-Sengers, Hessel
AU  - Peters-Sengers H
AD  - Center of Experimental & Molecular Medicine, Amsterdam University Medical 
      Centers, Location Academic Medical Center, University of Amsterdam, 1105 AZ 
      Amsterdam, the Netherlands.
FAU - Roelofs, Joris J T H
AU  - Roelofs JJTH
AD  - Amsterdam Infection & Immunity Institute, Amsterdam University Medical Centers, 
      Location Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the 
      Netherlands.
AD  - Department of Pathology, Amsterdam University Medical Centers, Location Academic 
      Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
FAU - de Vos, Alex F
AU  - de Vos AF
AD  - Center of Experimental & Molecular Medicine, Amsterdam University Medical 
      Centers, Location Academic Medical Center, University of Amsterdam, 1105 AZ 
      Amsterdam, the Netherlands.
AD  - Amsterdam Infection & Immunity Institute, Amsterdam University Medical Centers, 
      Location Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the 
      Netherlands.
FAU - van der Poll, Tom
AU  - van der Poll T
AD  - Center of Experimental & Molecular Medicine, Amsterdam University Medical 
      Centers, Location Academic Medical Center, University of Amsterdam, 1105 AZ 
      Amsterdam, the Netherlands.
AD  - Amsterdam Infection & Immunity Institute, Amsterdam University Medical Centers, 
      Location Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the 
      Netherlands.
AD  - Division of Infectious Diseases, Amsterdam University Medical Centers, Location 
      Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the 
      Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pathog Dis
JT  - Pathogens and disease
JID - 101595366
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Hif1a protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Hypoxia
MH  - Macrophages, Alveolar
MH  - Mice, Inbred C57BL
MH  - *Pneumonia, Pneumococcal/pathology
MH  - Streptococcus pneumoniae
MH  - Tumor Necrosis Factor-alpha
OTO - NOTNLM
OT  - Streptococcus pneumoniae
OT  - Hypoxia-inducible factor 1alpha
OT  - macrophages
OT  - neutrophils
OT  - pneumonia
EDAT- 2022/12/20 06:00
MHDA- 2023/01/27 06:00
CRDT- 2022/12/19 19:52
PHST- 2022/11/10 00:00 [received]
PHST- 2022/12/10 00:00 [revised]
PHST- 2022/12/17 00:00 [accepted]
PHST- 2022/12/20 06:00 [pubmed]
PHST- 2023/01/27 06:00 [medline]
PHST- 2022/12/19 19:52 [entrez]
AID - 6939823 [pii]
AID - 10.1093/femspd/ftac047 [doi]
PST - ppublish
SO  - Pathog Dis. 2023 Jan 17;81:ftac047. doi: 10.1093/femspd/ftac047.