Role of Hypoxia-inducible factor 1α in host defense during pneumococcal pneumonia.

Abstract

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.

• Authors: Liza Pereverzeva, Natasja A Otto, Hessel Peters-Sengers, Joris J T H Roelofs, Alex F de Vos, Tom van der Poll
• Journal: Pathogens and disease (Pathog Dis) Vol. 81 (01 17 2023) ISSN: 2049-632X [Electronic] United States
• PMID: 36535641 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.

Chemical References

• Tumor Necrosis Factor-alpha
• Hif1a protein, mouse

Topics

• Animals
• Mice
• Hypoxia
• Macrophages, Alveolar
• Mice, Inbred C57BL
• Pneumonia, Pneumococcal (pathology)
• Streptococcus pneumoniae
• Tumor Necrosis Factor-alpha