Contribution of HIV Infection, AIDS, and Antiretroviral Therapy to Exocrine Pathogenesis in Salivary and Lacrimal Glands

Nizamuddin, Imran; Koulen, Peter; McArthur, Carole

doi:10.3390/ijms19092747

Cited by 24 publications

(23 citation statements)

References 169 publications

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“…Most MiSGs contain mucus acini and secrete mucus saliva, which creates a protective lubricating micron-thick film that helps to avoid the subjective feeling of dry mouth [ 82 , 83 ]. Additionally, MiSGs produce saliva during sleep and therefore a decreased MiSG flow rate due to HIV/SIV induced inflammation may partially explain the night time dry mouth reported by HIV patients [ 84 , 85 , 86 ]. Although MiSGs contribute less than 10% of the saliva volume [ 82 , 83 ], they secrete high concentrations of immunoglobulin A that protects the oral mucosa from bacterial invasion [ 82 , 83 ].…”

Section: Discussionmentioning

confidence: 99%

Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus Macaques

Álvarez

Sestak

Byrareddy

et al. 2020

Viruses

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HIV/SIV-associated oral mucosal disease/dysfunction (HAOMD) (gingivitis/periodontitis/salivary adenitis) represents a major comorbidity affecting HIV patients on anti-retroviral therapy. Using a systems biology approach, we investigated molecular changes (mRNA/microRNA) underlying HAOMD and its modulation by phytocannabinoids (delta-9-tetrahydrocannabinol (∆9-THC)) in uninfected (n = 5) and SIV-infected rhesus macaques untreated (VEH-untreated/SIV; n = 7) or treated with vehicle (VEH/SIV; n = 3) or ∆9-THC (THC/SIV; n = 3). Relative to controls, fewer mRNAs were upregulated in THC/SIV compared to VEH-untreated/SIV macaques. Gene enrichment analysis showed differential enrichment of biological functions involved in anti-viral defense, Type-I interferon, Toll-like receptor, RIG-1 and IL1R signaling in VEH-untreated/SIV macaques. We focused on the anti-ER-stress anterior gradient-2 (AGR2), epithelial barrier protecting and anti-dysbiotic WAP Four-Disulfide Core Domain-2 (WFDC2) and glucocorticoid-induced anti-inflammatory TSC22D3 (TSC22-domain family member-3) that were significantly downregulated in oropharyngeal mucosa (OPM) of VEH-untreated/SIV macaques. All three proteins localized to minor salivary gland acini and secretory ducts and showed enhanced and reduced expression in OPM of THC/SIV and VEH/SIV macaques, respectively. Additionally, inflammation associated miR-21, miR-142-3p and miR-29b showed significantly higher expression in OPM of VEH-untreated/SIV macaques. TSC22D3 was validated as a target of miR-29b. These preliminary translational findings suggest that phytocannabinoids may safely and effectively reduce oral inflammatory responses in HIV/SIV and other (autoimmune) diseases.

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Section: Discussionmentioning

confidence: 99%

Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus Macaques

Álvarez

Sestak

Byrareddy

et al. 2020

Viruses

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“…A study showed that Fusobacterium , Campylobacter , Prevotella , Capnocytophaga , Selenomonas , Actinomyces , Granulicatella , and Atopobium were increased in HIV-infected individuals after receiving ART, while Aggregatibacter was significantly decreased. [ 45 ] Another study collected samples from 35 HIV-infected subjects at baseline and after 24 weeks of ART to compare the differences in oral microbiota. The results showed that the dominant phyla in samples from patients with 24 weeks of ART remained similar to those observed at baseline, and the diversity was not significantly different between samples collected at baseline and those collected after 24 weeks of ART.…”

Section: Effects Of Potential Interventions On the Oral Microbiomementioning

confidence: 99%

Alterations in the oral microbiome in HIV infection: causes, effects and potential interventions

et al. 2021

Chinese Medical Journal

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A massive depletion of CD4 + T lymphocytes has been described in early and acute human immunodeficiency virus (HIV) infection, leading to an imbalance between the human microbiome and immune responses. In recent years, a growing interest in the alterations in gut microbiota in HIV infection has led to many studies; however, only few studies have been conducted to explore the importance of oral microbiome in HIV-infected individuals. Evidence has indicated the dysbiosis of oral microbiota in people living with HIV (PLWH). Potential mechanisms might be related to the immunodeficiency in the oral cavity of HIV-infected individuals, including changes in secretory components such as reduced levels of enzymes and proteins in saliva and altered cellular components involved in the reduction and dysfunction of innate and adaptive immune cells. As a result, disrupted oral immunity in HIV-infected individuals leads to an imbalance between the oral microbiome and local immune responses, which may contribute to the development of HIV-related diseases and HIV-associated non-acquired immunodeficiency syndrome comorbidities. Although the introduction of antiretroviral therapy (ART) has led to a significant decrease in occurrence of the opportunistic oral infections in HIV-infected individuals, the dysbiosis in oral microbiome persists. Furthermore, several studies with the aim to investigate the ability of probiotics to regulate the dysbiosis of oral microbiota in HIV-infected individuals are ongoing. However, the effects of ART and probiotics on oral microbiome in HIV-infected individuals remain unclear. In this article, we review the composition of the oral microbiome in healthy and HIV-infected individuals and the possible effect of oral microbiome on HIV-associated oral diseases. We also discuss how ART and probiotics influence the oral microbiome in HIV infection. We believe that a deeper understanding of composition and function of the oral microbiome is critical for the development of effective preventive and therapeutic strategies for HIV infection.

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“…Oral microbiome turns to opportunistic pathogens that can lead to oral manifestations closely related to HIV/AIDS, such as oral candidiasis (OC) [3,6], oral hairy leukoplakia (OHL) [7,8], linear gingival erythema (LGE) [4,9], necrotizing ulcerative gingivitis (NUG), and necrotizing ulcerative periodontitis (NUP) [10]. In addition, through the HIV/AIDS onset, the use of antiretroviral therapy (ART) and psychological stress can trigger xerostomia in PLWHA [11,12]. Among other oral manifestations in HIV/AIDS patients, the most common is OC [3].…”

Section: Oral Innate Immunity In People Live With Hiv/aidsmentioning

confidence: 99%

Ellagic acid: an alternative for antifungal drugs resistance in HIV/AIDS patients with oropharyngeal candidiasis

Wicaksono¹,

Rezkita²,

Wijaya³

et al. 2020

HIV & AIDS Review

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Oropharyngeal candidiasis (OPC) is considered the most common fungal infection in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients. Antifungal drug, azole group, is the preferred treatment. However, the long-term use of antifungal drug as prophylaxis and therapy for OPC may lead to a compromised side effects and drug resistance. Nowadays, the prevalence of antifungal Candida albicans resistance is approximately 56.7%. Ellagic acid (EA) presents broad spectrum of antifungal activities. Based on previous studies, EA can act as natural antifungal agent. It also helps enhancing oral mucosal innate immunity. This review explores the antifungal activity of EA as an alternative for antifungal drugs resistance in HIV/AIDS patients with OPC. A web-based search was conducted via PubMed, NCBI, Scopus, ScienceDirect, and Research-Gate databases, with "antifungal resistance", "ellagic acid", "HIV/AIDS", and "OPC" as the keywords. EA is a dimeric derivative of gallic acid that is found in several plants. EA can induce the expression of hBD2 and SLPI in the oral mucosa. Those proteins play a pivotal role in immunomodulation and anti-inflammation of oral microenvironment innate immunity, which inhibit several opportunistic pathogens and microbes, including Candida. Furthermore, EA also inhibits ergosterol biosynthesis (EB), which is the primary component of fungi cell membrane. EA breakdown fungal membrane permeability and enzyme activity, leading to cessation of fungal growth. EA presents antifungal activity in HIV/AIDS patients with OPC; thus, it can be used as an alternative in antifungal drug resistance.

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Contribution of HIV Infection, AIDS, and Antiretroviral Therapy to Exocrine Pathogenesis in Salivary and Lacrimal Glands

Cited by 24 publications

References 169 publications

Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus Macaques

Long Term Delta-9-tetrahydrocannabinol Administration Inhibits Proinflammatory Responses in Minor Salivary Glands of Chronically Simian Immunodeficieny Virus Infected Rhesus Macaques

Alterations in the oral microbiome in HIV infection: causes, effects and potential interventions

Ellagic acid: an alternative for antifungal drugs resistance in HIV/AIDS patients with oropharyngeal candidiasis

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