Cannabidiol modulates expression of type I IFN response genes and HIV infection in macrophages

Shallu Tomer; Shallu Tomer; Wenli Mu; Wenli Mu; Gajendra Suryawanshi; Gajendra Suryawanshi; Hwee Ng; Hwee Ng; Li Wang; Li Wang; Wally Wennerberg; Wally Wennerberg; Valerie Rezek; Valerie Rezek; Heather Martin; Heather Martin; Irvin Chen; Irvin Chen; Scott Kitchen; Scott Kitchen; Anjie Zhen; Anjie Zhen

doi:10.3389/fimmu.2022.926696

Frontiers in Immunology (Sep 2022)

Cannabidiol modulates expression of type I IFN response genes and HIV infection in macrophages

Shallu Tomer,
Shallu Tomer,
Wenli Mu,
Wenli Mu,
Gajendra Suryawanshi,
Gajendra Suryawanshi,
Hwee Ng,
Hwee Ng,
Li Wang,
Li Wang,
Wally Wennerberg,
Wally Wennerberg,
Valerie Rezek,
Valerie Rezek,
Heather Martin,
Heather Martin,
Irvin Chen,
Irvin Chen,
Scott Kitchen,
Scott Kitchen,
Anjie Zhen,
Anjie Zhen

Affiliations

Shallu Tomer: Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Shallu Tomer: UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Wenli Mu: Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Wenli Mu: UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Gajendra Suryawanshi: UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Gajendra Suryawanshi: Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Hwee Ng: Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Hwee Ng: UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Li Wang: Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Li Wang: UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Wally Wennerberg: Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Wally Wennerberg: UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Valerie Rezek: Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Valerie Rezek: UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Heather Martin: Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Heather Martin: UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Irvin Chen: UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Irvin Chen: Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Scott Kitchen: Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Scott Kitchen: UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Anjie Zhen: Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States
Anjie Zhen: UCLA AIDS Institute and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States

DOI: https://doi.org/10.3389/fimmu.2022.926696
Journal volume & issue: Vol. 13

Abstract

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Cannabis (Cannabis sativa) is a widely used drug in the United States and the frequency of cannabis use is particularly high among people living with HIV (PLWH). One key component of cannabis, the non-psychotropic (−)-cannabidiol (CBD) exerts a wide variety of biological actions, including anticonvulsive, analgesic, and anti-inflammatory effects. However, the exact mechanism of action through which CBD affects the immune cell signaling remains poorly understood. Here we report that CBD modulates type I interferon responses in human macrophages. Transcriptomics analysis shows that CBD treatment significantly attenuates cGAS-STING-mediated activation of type I Interferon response genes (ISGs) in monocytic THP-1 cells. We further showed that CBD treatment effectively attenuates 2’3-cGAMP stimulation of ISGs in both THP-1 cells and primary human macrophages. Interestingly, CBD significantly upregulates expression of autophagy receptor p62/SQSTM1. p62 is critical for autophagy-mediated degradation of stimulated STING. We observed that CBD treated THP-1 cells have elevated autophagy activity. Upon 2’3’-cGAMP stimulation, CBD treated cells have rapid downregulation of phosphorylated-STING, leading to attenuated expression of ISGs. The CBD attenuation of ISGs is reduced in autophagy deficient THP-1 cells, suggesting that the effects of CBD on ISGs is partially mediated by autophagy induction. Lastly, CBD decreases ISGs expression upon HIV infection in THP-1 cells and human primary macrophages, leading to increased HIV RNA expression 24 hours after infection. However, long term culture with CBD in infected primary macrophages reduced HIV viral spread, suggesting potential dichotomous roles of CBD in HIV replication. Our study highlights the immune modulatory effects of CBD and the needs for additional studies on its effect on viral infection and inflammation.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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