Differential Signature of the Microbiome and Neutrophils in the Oral Cavity of HIV-Infected Individuals.

HIV infection is associated with a wide range of changes in microbial communities and immune cell components of the oral cavity. The purpose of this study was to evaluate the oral microbiome in relationship to oral neutrophils in HIV-infected compared to healthy individuals. We evaluated oral washes and saliva samples from HIV-infected individuals (n=52) and healthy controls (n=43). Using 16S-rRNA gene sequencing, we found differential ß-diversity using Principal Coordinate Analysis (PCoA) with Bray-Curtis distances. The α-diversity analysis by Faith's, Shannon, and observed OTUs indexes indicated that the saliva samples from HIV-infected individuals harbored significantly richer bacterial communities compared to the saliva samples from healthy individuals. Notably, we observed that five species of Spirochaeta including Spirochaetaceae, Spirochaeta, Treponema, Treponema amylovorum, and Treponema azotonutricum were significantly abundant. In contrast, Helicobacter species were significantly reduced in the saliva of HIV-infected individuals. Moreover, we found a significant reduction in the frequency of oral neutrophils in the oral cavity of HIV-infected individuals, which was positively related to their CD4+ T cell count. In particular, we noted a significant decline in CD44 expressing neutrophils and the intensity of CD44 expression on oral neutrophils of HIV-infected individuals. This observation was supported by the elevation of soluble CD44 in the saliva of HIV-infected individuals. Overall, the core oral microbiome was distinguishable between HIV-infected individuals on antiretroviral therapy compared to the HIV-negative group. The observed reduction in oral neutrophils might likely be related to the low surface expression of CD44, resulting in a higher bacterial diversity and richness in HIV-infected individuals.

HIV Infection and Compromised Mucosal Immunity: Oral Manifestations and Systemic Inflammation.

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.