TY - JOUR
T1 - Role of Hypoxia-inducible factor 1α in host defense during pneumococcal pneumonia
AU - Pereverzeva, Liza
AU - Otto, Natasja A.
AU - Peters-Sengers, Hessel
AU - Roelofs, Joris J. T. H.
AU - de Vos, Alex F.
AU - van der Poll, Tom
N1 - Funding Information: The authors Marieke S. ten Brink and Regina de Beer for excellent technical assistance with the experiments. LP was supported by Netherlands Organization for Health Research and Development, ZonMW, program JPIAMR [grant number 547001008]. NAO was supported by ZonMW [Grant number 40–00812-98–14016]. Publisher Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of FEMS. All rights reserved.
PY - 2023
Y1 - 2023
N2 - Hypoxia-inducible factor (HIF)1α is a transcription factor involved in cellular metabolism and regulation of immune cell effector functions. Here, we studied the role of HIF1α in myeloid cells during pneumonia caused by the major causative pathogen, Streptococcus pneumoniae (Spneu). Mice deficient for HIF1α in myeloid cells (LysMcreHif1αfl/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; HIF1α-deficiency in these cells was associated with diminished lactate release. In BMDMs, HIF1α-deficiency resulted in reduced secretion of tumor necrosis factor (TNF)α and interleukin (IL)-6 upon activation with Spneu but not LTA, while HIF1α-deficient AMs secreted less TNFα and IL-6 in response to LTA, and TNFα after Spneu stimulation. However, no difference was found in the host response of LysMcreHif1αfl/fl mice after Spneu infection as compared to controls. Similar in vivo findings were obtained in neutrophil (Mrp8creHif1αfl/fl) HIF1α-deficient mice. These data suggest that myeloid HIF1α is dispensable for the host defense during pneumococcal pneumonia.
AB - Hypoxia-inducible factor (HIF)1α is a transcription factor involved in cellular metabolism and regulation of immune cell effector functions. Here, we studied the role of HIF1α in myeloid cells during pneumonia caused by the major causative pathogen, Streptococcus pneumoniae (Spneu). Mice deficient for HIF1α in myeloid cells (LysMcreHif1αfl/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; HIF1α-deficiency in these cells was associated with diminished lactate release. In BMDMs, HIF1α-deficiency resulted in reduced secretion of tumor necrosis factor (TNF)α and interleukin (IL)-6 upon activation with Spneu but not LTA, while HIF1α-deficient AMs secreted less TNFα and IL-6 in response to LTA, and TNFα after Spneu stimulation. However, no difference was found in the host response of LysMcreHif1αfl/fl mice after Spneu infection as compared to controls. Similar in vivo findings were obtained in neutrophil (Mrp8creHif1αfl/fl) HIF1α-deficient mice. These data suggest that myeloid HIF1α is dispensable for the host defense during pneumococcal pneumonia.
KW - Hypoxia-inducible factor 1α
KW - Streptococcus pneumoniae
KW - macrophages
KW - neutrophils
KW - pneumonia
UR - http://www.scopus.com/inward/record.url?scp=85159065338&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/femspd/ftac047
DO - https://doi.org/10.1093/femspd/ftac047
M3 - Article
C2 - 36535641
SN - 2049-632X
VL - 81
JO - Pathogens and Disease
JF - Pathogens and Disease
M1 - ftac047
ER -