A Blunted GPR183/Oxysterol Axis during Dysglycemia Results in Delayed Recruitment of Macrophages to the Lung during Mycobacterium tuberculosis Infection

Research output: Contribution to journalJournal articleResearchpeer-review


  • Fulltext

    Final published version, 11.4 MB, PDF document

Background: We previously reported that reduced GPR183 expression in blood from tuberculosis (TB) patients with diabetes is associated with more severe TB. Methods: To further elucidate the role of GPR183 and its oxysterol ligands in the lung, we studied dysglycemic mice infected with Mycobacterium tuberculosis (Mtb). Results: We found upregulation of the oxysterol-producing enzymes CH25H and CYP7B1 and increased concentrations of 25-hydroxycholesterol upon Mtb infection in the lungs of mice. This was associated with increased expression of GPR183 indicative of oxysterol-mediated recruitment of GPR183-expressing immune cells to the lung. CYP7B1 was predominantly expressed by macrophages in TB granulomas. CYP7B1 expression was significantly blunted in lungs from dysglycemic animals, which coincided with delayed macrophage infiltration. GPR183-deficient mice similarly had reduced macrophage recruitment during early infection. Conclusions: Taken together, we demonstrate a requirement of the GPR183/oxysterol axis for positioning of macrophages to the site of infection and add an explanation to more severe TB in diabetes patients.

Original languageEnglish
JournalJournal of Infectious Diseases
Issue number12
Pages (from-to)2219-2228
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.

    Research areas

  • 25-hydroxycholesterol, diabetes, GPR183, oxysterols, tuberculosis

Number of downloads are based on statistics from Google Scholar and www.ku.dk

No data available

ID: 314066528