Cannabinoid control of gingival immune activation in chronically SIV-infected rhesus macaques involves modulation of the indoleamine-2,3-dioxygenase-1 pathway and salivary microbiome.
HIVSIV-associated periodontal disease (gingivitisperiodontitis) (PD) represents a major comorbidity affecting people living with HIV (PLWH) on combination anti-retroviral therapy (cART). PD is characterized by chronic inflammation and dysbiosis. Nevertheless, the molecular mechanisms and use of feasible therapeutic strategies to reducereverse inflammation and dysbiosis remain understudied and unaddressed. Employing a systems biology approach, we report molecular, metabolome and microbiome changes underlying PD and its modulation by phytocannabinoids delta-9-tetrahydrocannabinol (Δ VEH- untreatedSIV but not THCSIV RMs showed significant enrichment of genes linked to anti-viral defense, interferon-β, NFκB, RIG-1, and JAK-STAT signaling. We focused on the anti-microbial DUOX1 and immune activation marker IDO1 that were reciprocally regulated in the gingiva of VEH-untreatedSIV RMs. Both proteins localized to the gingival epithelium and CD163 The data provides deeper insights into the molecular mechanisms underlying HIVSIV-induced PD and more importantly, the anti-inflammatory and anti-dysbiotic properties of THC in the oral cavity. Overall, these translational findings suggest that phytocannabinoids may help reduce gingivalsystemic inflammation, salivary dysbiosis and potentially metabolic diseasesyndrome in PLWH on cART and those with no access to cART or do not suppress the virus under cART. Research reported in this publication was supported by the National Institutes of Health Award Numbers R01DA052845 (MM and SNB), R01DA050169 (MM and CO), R01DA042524 and R56DE026930 (MM), and P51OD011104 and P51OD011133. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.