Innate immune mechanisms to oral pathogens in oral mucosa of HIV-infected individuals.

Aaron Weinberg,Srabanti Rakshit,Sharof Tugizov,Annapurna Vyakarnam,Ge Jin,Julian R Naglik,Pushpa Pandiyan

doi:10.1111/odi.13470

Abstract

A crucial aspect of mucosal HIV transmission is the interaction between HIV, the local environmental milieu and immune cells. The oral mucosa comprises many host cell types including epithelial cells, CD4 + T cells, dendritic cells and monocytes/macrophages, as well as a diverse microbiome predominantly comprising bacterial species. While the oral epithelium is one of the first sites exposed to HIV through oral-genital contact and nursing infants, it is largely thought to be resistant to HIV transmission via mechanisms that are still unclear. HIV-1 infection is also associated with predisposition to secondary infections, such as tuberculosis, and other diseases including cancer. This review addresses the following questions that were discussed at the 8th World Workshop on Oral Health and Disease in AIDS held in Bali, Indonesia, 13 September –15 September 2019: (a) How does HIV infection affect epithelial cell signalling? (b) How does HIV infection affect the production of cytokines and other innate antimicrobial factors, (c) How is the mucosal distribution and function of immune cells altered in HIV infection? (d) How do T cells affect HIV (oral) pathogenesis and cancer? (e) How does HIV infection lead to susceptibility to TB infections?

Highlights

The oral epithelium is a complex structure that provides the first line of innate immune defence against HIV infection (Levy, 2001)
HIV gp120 interacts with galactosylceramide (GalCer) and chemokine receptors CCR5 and/or CXCR4 on the oral, genital and intestinal epithelial surface (Herrera et al, 2016; Kohli et al, 2014; Tugizov et al, 2011; Yasen, Herrera, Rosbe, Lien, & Tugizov, 2018)
HIV gp120-induced activation of mitogenactivated protein kinase (MAPK) and disruption of oral and genital mucosal epithelial cells may play a critical role in the paracellular penetration of virus upon primary infection (Nazli et al, 2010), which may initiate the systemic HIV/ AIDS disease

Summary

Introduction

The oral epithelium is a complex structure that provides the first line of innate immune defence against HIV infection (Levy, 2001). Recent developments in microbiome studies further complicate this complex relationship, as HIV-1 integration/infection of local mucosal epithelial and/or immune cells may predispose individuals to secondary infections and other diseases such as cancer.

Results

Conclusion