Cholesterol Regulates Innate Immunity via Nuclear Hormone Receptor NHR-8

Benson Otarigho; Alejandro Aballay

doi:10.1016/j.isci.2020.101068

Cholesterol Regulates Innate Immunity via Nuclear Hormone Receptor NHR-8

iScience. 2020 May 22;23(5):101068. doi: 10.1016/j.isci.2020.101068. Epub 2020 Apr 18.

Authors

Benson Otarigho¹, Alejandro Aballay²

Affiliations

¹ Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR 97239, USA.
² Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: aballay@ohsu.edu.

Abstract

Cholesterol is an essential nutrient for the function of diverse biological processes and for steroid biosynthesis across metazoans. However, the role of cholesterol in immune function remains understudied. Using the nematode Caenorhabditis elegans, which depends on the external environment for cholesterol, we studied the relationship between cholesterol and innate immunity. We found that the transporter CHUP-1 is required for the effect of cholesterol in the development of innate immunity and that the cholesterol-mediated immune response requires the nuclear hormone receptor NHR-8. Cholesterol acts through NHR-8 to transcriptionally regulate immune genes that are controlled by conserved immune pathways, including a p38/PMK-1 MAPK pathway, a DAF-2/DAF-16 insulin pathway, and an Nrf/SKN-1 pathway. Our results indicate that cholesterol plays a key role in the activation of conserved microbicidal pathways that are essential for survival against bacterial infections.

Keywords: Biochemistry; Immunity; Microbial Metabolism.

Abstract

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