GPR183 Regulates Interferons, Autophagy, and Bacterial Growth During Mycobacterium tuberculosis Infection and Is Associated With TB Disease Severity

Research output: Contribution to journal › Journal article › Research › peer-review

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GPR183 Regulates Interferons, Autophagy, and Bacterial Growth During Mycobacterium tuberculosis Infection and Is Associated With TB Disease Severity. / Bartlett, Stacey; Gemiarto, Adrian Tandhyka; Ngo, Minh Dao; Sajiir, Haressh; Hailu, Semira; Sinha, Roma; Foo, Cheng Xiang; Kleynhans, Leanie; Tshivhula, Happy; Webber, Tariq; Bielefeldt-Ohmann, Helle; West, Nicholas P.; Hiemstra, Andriette M.; MacDonald, Candice E.; Christensen, Liv von Voss; Schlesinger, Larry S.; Walzl, Gerhard; Rosenkilde, Mette Marie; Mandrup-Poulsen, Thomas; Ronacher, Katharina.

In: Frontiers in Immunology, Vol. 11, 601534, 2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Bartlett, S, Gemiarto, AT, Ngo, MD, Sajiir, H, Hailu, S, Sinha, R, Foo, CX, Kleynhans, L, Tshivhula, H, Webber, T, Bielefeldt-Ohmann, H, West, NP, Hiemstra, AM, MacDonald, CE, Christensen, LVV, Schlesinger, LS, Walzl, G, Rosenkilde, MM, Mandrup-Poulsen, T & Ronacher, K 2020, 'GPR183 Regulates Interferons, Autophagy, and Bacterial Growth During Mycobacterium tuberculosis Infection and Is Associated With TB Disease Severity', Frontiers in Immunology, vol. 11, 601534. https://doi.org/10.3389/fimmu.2020.601534

APA

Bartlett, S., Gemiarto, A. T., Ngo, M. D., Sajiir, H., Hailu, S., Sinha, R., Foo, C. X., Kleynhans, L., Tshivhula, H., Webber, T., Bielefeldt-Ohmann, H., West, N. P., Hiemstra, A. M., MacDonald, C. E., Christensen, L. V. V., Schlesinger, L. S., Walzl, G., Rosenkilde, M. M., Mandrup-Poulsen, T., & Ronacher, K. (2020). GPR183 Regulates Interferons, Autophagy, and Bacterial Growth During Mycobacterium tuberculosis Infection and Is Associated With TB Disease Severity. Frontiers in Immunology, 11, [601534]. https://doi.org/10.3389/fimmu.2020.601534

Vancouver

Bartlett S, Gemiarto AT, Ngo MD, Sajiir H, Hailu S, Sinha R et al. GPR183 Regulates Interferons, Autophagy, and Bacterial Growth During Mycobacterium tuberculosis Infection and Is Associated With TB Disease Severity. Frontiers in Immunology. 2020;11. 601534. https://doi.org/10.3389/fimmu.2020.601534

Author

Bartlett, Stacey ; Gemiarto, Adrian Tandhyka ; Ngo, Minh Dao ; Sajiir, Haressh ; Hailu, Semira ; Sinha, Roma ; Foo, Cheng Xiang ; Kleynhans, Leanie ; Tshivhula, Happy ; Webber, Tariq ; Bielefeldt-Ohmann, Helle ; West, Nicholas P. ; Hiemstra, Andriette M. ; MacDonald, Candice E. ; Christensen, Liv von Voss ; Schlesinger, Larry S. ; Walzl, Gerhard ; Rosenkilde, Mette Marie ; Mandrup-Poulsen, Thomas ; Ronacher, Katharina. / GPR183 Regulates Interferons, Autophagy, and Bacterial Growth During Mycobacterium tuberculosis Infection and Is Associated With TB Disease Severity. In: Frontiers in Immunology. 2020 ; Vol. 11.

Bibtex

@article{70ac1e7763e9492486a7454d83cb2ac9,
title = "GPR183 Regulates Interferons, Autophagy, and Bacterial Growth During Mycobacterium tuberculosis Infection and Is Associated With TB Disease Severity",
abstract = "Oxidized cholesterols have emerged as important signaling molecules of immune function, but little is known about the role of these oxysterols during mycobacterial infections. We found that expression of the oxysterol-receptor GPR183 was reduced in blood from patients with tuberculosis (TB) and type 2 diabetes (T2D) compared to TB patients without T2D and was associated with TB disease severity on chest x-ray. GPR183 activation by 7 alpha,25-dihydroxycholesterol (7 alpha,25-OHC) reduced growth of Mycobacterium tuberculosis (Mtb) and Mycobacterium bovis BCG in primary human monocytes, an effect abrogated by the GPR183 antagonist GSK682753. Growth inhibition was associated with reduced IFN-beta and IL-10 expression and enhanced autophagy. Mice lacking GPR183 had significantly increased lung Mtb burden and dysregulated IFNs during early infection. Together, our data demonstrate that GPR183 is an important regulator of intracellular mycobacterial growth and interferons during mycobacterial infection.",
keywords = "Mycobacterium tuberculosis, diabetes, oxysterols, 7 alpha,25-dihydroxycholesterol, GPR183, EBI2, host-direct therapies, autophagy, RECEPTOR EBI2, 7-TRANSMEMBRANE RECEPTOR, CONVERGING EPIDEMICS, IL-1-BETA PRODUCTION, RESEARCH AGENDA, I INTERFERONS, OXYSTEROLS, MIGRATION, IDENTIFICATION, MACROPHAGES",
author = "Stacey Bartlett and Gemiarto, {Adrian Tandhyka} and Ngo, {Minh Dao} and Haressh Sajiir and Semira Hailu and Roma Sinha and Foo, {Cheng Xiang} and Leanie Kleynhans and Happy Tshivhula and Tariq Webber and Helle Bielefeldt-Ohmann and West, {Nicholas P.} and Hiemstra, {Andriette M.} and MacDonald, {Candice E.} and Christensen, {Liv von Voss} and Schlesinger, {Larry S.} and Gerhard Walzl and Rosenkilde, {Mette Marie} and Thomas Mandrup-Poulsen and Katharina Ronacher",
year = "2020",
doi = "10.3389/fimmu.2020.601534",
language = "English",
volume = "11",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - GPR183 Regulates Interferons, Autophagy, and Bacterial Growth During Mycobacterium tuberculosis Infection and Is Associated With TB Disease Severity

AU - Bartlett, Stacey

AU - Gemiarto, Adrian Tandhyka

AU - Ngo, Minh Dao

AU - Sajiir, Haressh

AU - Hailu, Semira

AU - Sinha, Roma

AU - Foo, Cheng Xiang

AU - Kleynhans, Leanie

AU - Tshivhula, Happy

AU - Webber, Tariq

AU - Bielefeldt-Ohmann, Helle

AU - West, Nicholas P.

AU - Hiemstra, Andriette M.

AU - MacDonald, Candice E.

AU - Christensen, Liv von Voss

AU - Schlesinger, Larry S.

AU - Walzl, Gerhard

AU - Rosenkilde, Mette Marie

AU - Mandrup-Poulsen, Thomas

AU - Ronacher, Katharina

PY - 2020

Y1 - 2020

N2 - Oxidized cholesterols have emerged as important signaling molecules of immune function, but little is known about the role of these oxysterols during mycobacterial infections. We found that expression of the oxysterol-receptor GPR183 was reduced in blood from patients with tuberculosis (TB) and type 2 diabetes (T2D) compared to TB patients without T2D and was associated with TB disease severity on chest x-ray. GPR183 activation by 7 alpha,25-dihydroxycholesterol (7 alpha,25-OHC) reduced growth of Mycobacterium tuberculosis (Mtb) and Mycobacterium bovis BCG in primary human monocytes, an effect abrogated by the GPR183 antagonist GSK682753. Growth inhibition was associated with reduced IFN-beta and IL-10 expression and enhanced autophagy. Mice lacking GPR183 had significantly increased lung Mtb burden and dysregulated IFNs during early infection. Together, our data demonstrate that GPR183 is an important regulator of intracellular mycobacterial growth and interferons during mycobacterial infection.

AB - Oxidized cholesterols have emerged as important signaling molecules of immune function, but little is known about the role of these oxysterols during mycobacterial infections. We found that expression of the oxysterol-receptor GPR183 was reduced in blood from patients with tuberculosis (TB) and type 2 diabetes (T2D) compared to TB patients without T2D and was associated with TB disease severity on chest x-ray. GPR183 activation by 7 alpha,25-dihydroxycholesterol (7 alpha,25-OHC) reduced growth of Mycobacterium tuberculosis (Mtb) and Mycobacterium bovis BCG in primary human monocytes, an effect abrogated by the GPR183 antagonist GSK682753. Growth inhibition was associated with reduced IFN-beta and IL-10 expression and enhanced autophagy. Mice lacking GPR183 had significantly increased lung Mtb burden and dysregulated IFNs during early infection. Together, our data demonstrate that GPR183 is an important regulator of intracellular mycobacterial growth and interferons during mycobacterial infection.

KW - Mycobacterium tuberculosis

KW - diabetes

KW - oxysterols

KW - 7 alpha,25-dihydroxycholesterol

KW - GPR183

KW - EBI2

KW - host-direct therapies

KW - autophagy

KW - RECEPTOR EBI2

KW - 7-TRANSMEMBRANE RECEPTOR

KW - CONVERGING EPIDEMICS

KW - IL-1-BETA PRODUCTION

KW - RESEARCH AGENDA

KW - I INTERFERONS

KW - OXYSTEROLS

KW - MIGRATION

KW - IDENTIFICATION

KW - MACROPHAGES

U2 - 10.3389/fimmu.2020.601534

DO - 10.3389/fimmu.2020.601534

M3 - Journal article

C2 - 33240287

VL - 11

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 601534

ER -

ID: 257026783