Abstract

Mucosal surfaces account for the vast majority of HIV transmission. In adults, HIV transmission occurs mainly by vaginal and rectal routes but rarely via oral route. By contrast, pediatric HIV infections could be as the result of oral route by breastfeeding. As such mucosal surfaces play a crucial role in HIV acquisition, and spread of the virus depends on its ability to cross a mucosal barrier. HIV selectively infects, depletes, and/or dysregulates multiple arms of the human immune system particularly at the mucosal sites and causes substantial irreversible damage to the mucosal barriers. This leads to microbial products translocation and subsequently hyper-immune activation. Although introduction of antiretroviral therapy (ART) has led to significant reduction in morbidity and mortality of HIV-infected patients, viral replication persists. As a result, antigen presence and immune activation are linked to “inflammaging” that attributes to a pro-inflammatory environment and the accelerated aging process in HIV patients. HIV infection is also associated with the prevalence of oral mucosal infections and dysregulation of oral microbiota, both of which may compromise the oral mucosal immunity of HIV-infected individuals. In addition, impaired oral immunity in HIV infection may predispose the patients to periodontal diseases that are associated with systemic inflammation and increased risk of cardiovascular diseases. The purpose of this review is to examine existing evidence regarding the role of innate and cellular components of the oral cavity in HIV infection and how HIV infection may drive systemic hyper-immune activation in these patients. We will also discuss current knowledge on HIV oral transmission, HIV immunosenescence in relation to the oral mucosal alterations during the course of HIV infection and periodontal disease. Finally, we discuss oral manifestations associated with HIV infection and how HIV infection and ART influence the oral microbiome. Therefore, unraveling how HIV compromises the integrity of the oral mucosal tissues and innate immune components of the oral cavity and its association with induction of chronic inflammation are critical for the development of effective preventive interventions and therapeutic strategies.

Highlights

  • HIV infection continues to be a major global health issue with an estimated 36.7 million people living with HIV worldwide [1]

  • This review focuses on the innate immune components of the oral cavity with regard to HIV infection, the key markers associated with periodontal disease, the current understanding of oral inflammation in HIV infection, as well as evaluates interventions that might be utilized to improve oral health of HIV-infected individuals

  • We propose that periodontitis and/or compromised oral immune system associated with HIV infection may result in a local inflammatory condition and microbial products translocation that leads to systemic inflammation (Figure 3)

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Summary

INTRODUCTION

HIV infection continues to be a major global health issue with an estimated 36.7 million people living with HIV worldwide [1]. Oral mucosal immune cells express a wide range of pathogen-recognition receptors (PRRs) and metabolic sensors that act either as suppressors or activators [17] It is unclear whether immunological changes following HIV infection compromise the integrity of physical barrier in the oral cavity and enhance microbial products translocation, which subsequently contribute in the induction of chronic inflammation. Periodontal disease is common among adults and characterized by chronic inflammation of the oral mucosa This disease is caused by the interplay between the pathogenic microorganisms and host defense that can lead to microbial translocation and increased risk of inflammatory conditions, such as CVD [18, 19]. This review focuses on the innate immune components of the oral cavity with regard to HIV infection, the key markers associated with periodontal disease, the current understanding of oral inflammation in HIV infection, as well as evaluates interventions that might be utilized to improve oral health of HIV-infected individuals

INNATE IMMUNE COMPONENTS OF SALIVA
Secretory IgA
Levels in saliva
INNATE IMMUNE COMPONENTS OF THE ORAL CAVITY AND HIV
Plasmacytoid DCs
ORAL TRANSMISSION OF HIV
ORAL MUCOSAL INFECTIONS AND HIV INFECTION
HIV AND ORAL MICROBIOME
PERIODONTAL DISEASE AND SYSTEMIC INFLAMMATION
HIV AND IMMUNOSENESCENCE
Findings
CONCLUDING REMARKS
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