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

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A Blunted GPR183/Oxysterol Axis during Dysglycemia Results in Delayed Recruitment of Macrophages to the Lung during Mycobacterium tuberculosis Infection. / Ngo, Minh Dao; Bartlett, Stacey; Bielefeldt-Ohmann, Helle; Foo, Cheng Xiang; Sinha, Roma; Arachchige, Buddhika Jayakody; Reed, Sarah; Mandrup-Poulsen, Thomas; Rosenkilde, Mette Marie; Ronacher, Katharina.

In: Journal of Infectious Diseases, Vol. 225, No. 12, 2022, p. 2219-2228.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Ngo, MD, Bartlett, S, Bielefeldt-Ohmann, H, Foo, CX, Sinha, R, Arachchige, BJ, Reed, S, Mandrup-Poulsen, T, Rosenkilde, MM & Ronacher, K 2022, 'A Blunted GPR183/Oxysterol Axis during Dysglycemia Results in Delayed Recruitment of Macrophages to the Lung during Mycobacterium tuberculosis Infection', Journal of Infectious Diseases, vol. 225, no. 12, pp. 2219-2228. https://doi.org/10.1093/infdis/jiac102

APA

Ngo, M. D., Bartlett, S., Bielefeldt-Ohmann, H., Foo, C. X., Sinha, R., Arachchige, B. J., Reed, S., Mandrup-Poulsen, T., Rosenkilde, M. M., & Ronacher, K. (2022). A Blunted GPR183/Oxysterol Axis during Dysglycemia Results in Delayed Recruitment of Macrophages to the Lung during Mycobacterium tuberculosis Infection. Journal of Infectious Diseases, 225(12), 2219-2228. https://doi.org/10.1093/infdis/jiac102

Vancouver

Ngo MD, Bartlett S, Bielefeldt-Ohmann H, Foo CX, Sinha R, Arachchige BJ et al. A Blunted GPR183/Oxysterol Axis during Dysglycemia Results in Delayed Recruitment of Macrophages to the Lung during Mycobacterium tuberculosis Infection. Journal of Infectious Diseases. 2022;225(12):2219-2228. https://doi.org/10.1093/infdis/jiac102

Author

Ngo, Minh Dao ; Bartlett, Stacey ; Bielefeldt-Ohmann, Helle ; Foo, Cheng Xiang ; Sinha, Roma ; Arachchige, Buddhika Jayakody ; Reed, Sarah ; Mandrup-Poulsen, Thomas ; Rosenkilde, Mette Marie ; Ronacher, Katharina. / A Blunted GPR183/Oxysterol Axis during Dysglycemia Results in Delayed Recruitment of Macrophages to the Lung during Mycobacterium tuberculosis Infection. In: Journal of Infectious Diseases. 2022 ; Vol. 225, No. 12. pp. 2219-2228.

Bibtex

@article{c9d0a6e5a9b2448eb7a0568ef4c364b9,
title = "A Blunted GPR183/Oxysterol Axis during Dysglycemia Results in Delayed Recruitment of Macrophages to the Lung during Mycobacterium tuberculosis Infection",
abstract = "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. ",
keywords = "25-hydroxycholesterol, diabetes, GPR183, oxysterols, tuberculosis",
author = "Ngo, {Minh Dao} and Stacey Bartlett and Helle Bielefeldt-Ohmann and Foo, {Cheng Xiang} and Roma Sinha and Arachchige, {Buddhika Jayakody} and Sarah Reed and Thomas Mandrup-Poulsen and Rosenkilde, {Mette Marie} and Katharina Ronacher",
note = "Publisher Copyright: {\textcopyright} 2022 The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.",
year = "2022",
doi = "10.1093/infdis/jiac102",
language = "English",
volume = "225",
pages = "2219--2228",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "12",

}

RIS

TY - JOUR

T1 - A Blunted GPR183/Oxysterol Axis during Dysglycemia Results in Delayed Recruitment of Macrophages to the Lung during Mycobacterium tuberculosis Infection

AU - Ngo, Minh Dao

AU - Bartlett, Stacey

AU - Bielefeldt-Ohmann, Helle

AU - Foo, Cheng Xiang

AU - Sinha, Roma

AU - Arachchige, Buddhika Jayakody

AU - Reed, Sarah

AU - Mandrup-Poulsen, Thomas

AU - Rosenkilde, Mette Marie

AU - Ronacher, Katharina

N1 - Publisher Copyright: © 2022 The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - 25-hydroxycholesterol

KW - diabetes

KW - GPR183

KW - oxysterols

KW - tuberculosis

UR - http://www.scopus.com/inward/record.url?scp=85132454687&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiac102

DO - 10.1093/infdis/jiac102

M3 - Journal article

C2 - 35303091

AN - SCOPUS:85132454687

VL - 225

SP - 2219

EP - 2228

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 12

ER -

ID: 314066528