GPR183 Regulates Interferons, Autophagy, and Bacterial Growth During Mycobacterium tuberculosis Infection and Is Associated With TB Disease Severity
Year: 2020
Type: article
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 7α,25-hydroxycholesterol (7α,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-β 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. Graphical Abstract
Source: Frontiers in Immunology
Authors: Stacey Bartlett, Adrian Tandhyka Gemiarto, Minh Dao Ngo, Haressh Sajiir, Semira Hailu, Roma Sinha, Cheng Xiang Foo, Léanie Kleynhans, Happy Tshivhula, Tariq Webber, Helle Bielefeldt-Ohmann, Nicholas P. West, Andriette M. Hiemstra, Candice E. MacDonald, Liv von Voss Christensen, Larry S. Schlesinger, Gerhard Walzl, Mette Marie Rosenkilde, Thomas Mandrup-Poulsen, Katharina Ronacher
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: Mater Foundation, Australian Government, European Commission, Australian Respiratory Council, South African Medical Research Council, Novo Nordisk, Universiteit Stellenbosch, Novo Nordisk Fonden, National Institutes of Health, Medical Research Council, Seventh Framework Programme, National Institute of Allergy and Infectious Diseases
OpenAlex ID: W3097643358