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

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.

Plasma levels of soluble membrane attack complex are elevated despite viral suppression in HIV patients with poor immune reconstitution

“…While viral replication is effectively suppressed with ART, systemic inflammation persists from cell‐to‐cell viral transfer, microbial translocation of bacteria and viral co‐infections such as cytomegalovirus (CMV) and herpes simplex virus (HSV) (reviewed in ). Because microbial translocation of proinflammatory bacterial products drives systemic inflammation , we postulated that this may activate the complement cascade. Thus, we sought to determine if sMAC levels were altered in ART‐treated, virally suppressed PLWH (ART‐VS‐PLWH) due potentially to pathogen by‐product‐mediated complement activation.…”

Biomarkers of oral inflammation in perinatally HIV‐infected and perinatally HIV‐exposed, uninfected youth

“…It has been suggested that these biomarkers can be used to predict which patients will have progressive disease (Tomas et al, 2017). Unfortunately, more advanced periodontal disease is common in adults with HIV (Heron & Elahi, 2017;Ryder, Nittayananta, Coogan, Greenspan, & Greenspan, 2012). Since little is known regarding PHIV youth and biomarkers of disease progression, follow-up of this cohort will be essential and is currently underway.…”

Oral bacteriome of HIV‐1‐infected children from Rio de Janeiro, Brazil: Next‐generation DNA sequencing analysis

“…This is in agreement with Dang et al, 2012, who also showed an impact of the HIV-1 infection on the dorsal tongue microbiota, albeit in untreated HIV-1-infected adults. The effect of HIV-1 infection in the subgingival and tongue sites could be associated with the CD4+ T-cell depletion and consequence decrease of T-cell-associated cytokines, including IL-17 and IL-23, which play a role in the protection against mucosal candidiasis (Huppler et al, 2014) and other opportunistic infections (Heron & Elahi, 2017). In addition, Notch-1 signalling mediates oral epithelial cell differentiation (Casey et al, 2006) and regulates the activity of CD4+ T-cell responses by promoting cellular longevity (Helbig et al, 2012).…”

“…It has been proposed that HIV-1 infection is associated with alterations in the gut microbiome. These occur early in the course of infection, as a consequence of the depletion of CD4+ T cells in the intestinal mucosa, and are not fully restored with antiretroviral therapy (Brenchley, 2013;Heron & Elahi, 2017;Saxena et al, 2016;Zevin, McKinnon, Burgener, & Klatt, 2016). Whether similar changes occur in the oral microbiome are, as yet, unknown.…”