Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

HIV-Induced Modulation of TREM2 Expression Is Reversed by Cannabidiol: Implications for Age-Related Neuropathogenesis in People with HIV

Bryant Avalos
,
Jacqueline R Kulbe
,
Mary Ford
,
Anna Elizabeth Laird
,
Kyle Walter
,
Michael Mante
,
Jazmin Florio
,
Ali Boustani
ORCID logo ,
Antoine Chaillon
ORCID logo ,
Johannes Schlachetzki
,
Erin Sundermann
ORCID logo ,
David Volsky
,
Robert A Rissman
,
Ronald Ellis
ORCID logo ,
Scott Letendre
,
Jennifer Iudicello
,
Jerel Adam Fields
*
Version 1 : Received: 13 August 2024 / Approved: 13 August 2024 / Online: 13 August 2024 (08:56:20 CEST)

How to cite: Avalos, B.; Kulbe, J. R.; Ford, M.; Laird, A. E.; Walter, K.; Mante, M.; Florio, J.; Boustani, A.; Chaillon, A.; Schlachetzki, J.; Sundermann, E.; Volsky, D.; Rissman, R. A.; Ellis, R.; Letendre, S.; Iudicello, J.; Fields, J. A. HIV-Induced Modulation of TREM2 Expression Is Reversed by Cannabidiol: Implications for Age-Related Neuropathogenesis in People with HIV. Preprints 2024, 2024080904. https://doi.org/10.20944/preprints202408.0904.v1 Avalos, B.; Kulbe, J. R.; Ford, M.; Laird, A. E.; Walter, K.; Mante, M.; Florio, J.; Boustani, A.; Chaillon, A.; Schlachetzki, J.; Sundermann, E.; Volsky, D.; Rissman, R. A.; Ellis, R.; Letendre, S.; Iudicello, J.; Fields, J. A. HIV-Induced Modulation of TREM2 Expression Is Reversed by Cannabidiol: Implications for Age-Related Neuropathogenesis in People with HIV. Preprints 2024, 2024080904. https://doi.org/10.20944/preprints202408.0904.v1

Abstract

(1) Background: Triggering receptor expressed on myeloid cells 2 (TREM2) is involved in neu-roinflammation and HIV-associated neurocognitive impairment (NCI). People with HIV (PWH) using cannabis exhibit lower inflammation and neurological disorders. We hypothesized TREM2 dysfunction mediates HIV neuropathogenesis and can be reversed by cannabinoids. (2) Methods: EcoHIV-infected wildtype (WT) and TREM2R47H mutant mice were used to study HIV's impact on TREM2 and behavior. TREM2 and related gene expressions were examined in mono-cyte-derived macrophages (MDMs) from PWH (n=42) and people without HIV (PWoH; n=19) with varying cannabis use via RNA sequencing and qPCR. Differences in membrane-bound and soluble TREM2 (sTREM2) were evaluated using immunocytochemistry (ICC) and ELISA. (3) Results: EcoHIV increased immature and C-terminal fragment forms of TREM2 in WT mice but not in TREM2R47H mice, with increased IBA1 protein in TREM2R47H hippocampi, correlating with worse memory test performance. TREM2 mRNA levels increased with age in PWoH but not PWH. Cannabidiol (CBD) treatment increased TREM2 mRNA alone and with IL1β. RNA-seq showed upregulation of TREM2-related transcripts in cannabis-using PWH compared to naïve controls. IL1β increased sTREM2 and reduced membrane-bound TREM2, effects partially re-versed by CBD. (4) Conclusions: These findings suggest HIV affects TREM2 expression modu-lated by cannabis and CBD, offering insights for therapeutic strategies.

Keywords

TREM2; HIV; neuroinflammation; cannabis; immunomodulatory; CBD

Subject

Biology and Life Sciences, Aging

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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