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Immunopathogenesis of HIV/AIDS-related Oral Manifestations and Host Immunity

Integrative Biology and Infectious Diseases Branch
Division of Extramural Research


OBJECTIVE:

The goal of this initiative is to support research on: i) non-pathogenic and immunopathogenic events that occur early in HIV and AIDS-related oral opportunistic infections; ii) pathogen interactions in the oral cavity that induce lesions and disease exacerbation; iii) oral host immune responses to HIV and oral opportunistic pathogens that lessen the pathogenic effects of infection or induce remission of oral lesions; and iv) oral host immune responses to oral mucosal prophylactic HIV vaccines or oral therapies to treat opportunistic infections.  An expected outcome of this initiative is the generation of knowledge to guide translational research on the development of novel, oral mucosal prophylactic HIV vaccines and therapeutic strategies for oral opportunistic infections.

 

BACKGROUND:

The oral mucosa is one of the major sites for HIV penetration with infrequent transmission, but with potential for systemic spread. HIV infection is accompanied by AIDS-related oral manifestations, occurring in almost all cases worldwide. Even after antiretroviral therapy, oral manifestations of HIV/AIDS still represent a major public health problem. Based on this, it is essential to develop novel preventive and therapeutic approaches, including the design of safe and efficacious oral mucosal prophylactic HIV vaccines and innovative oral therapies against oral opportunistic pathogens. In order to develop these approaches, a comprehensive understanding of the non-immunopathogenic and immunopathogenic events that occur early during HIV infection and transmission, and during secondary infection caused by oral opportunistic pathogens is needed. The successful development of prophylactic and therapeutic approaches also depends on a thorough understanding of oral HIV vaccine-induced and oral pathogen-induced innate, mucosal, and adaptive immune responses. These host responses are essential to blocking early events during infection and transmission, decreasing oral pathogen load, and containing infections in the oral cavity, and ultimately decreasing pathology and clinical manifestations. 

From a pathogenesis perspective, progress has been made in understanding some aspects of the immunopathogenesis of HIV and its associated opportunistic infections as well as in deciphering some elements of the host immune responses against these infections. For instance, general knowledge has been gained regarding the dual role of the oral mucosal epithelium acting as a barrier and as a main portal of pathogen entry; events that occur during oral mucosal infection, local dissemination and systemic transmission; and disease exacerbation by inflammation and laceration. From a prevention perspective, some studies conducted in animals and humans have shown that immune responses (innate, mucosal, and adaptive immunity) can be triggered with HIV prophylactic vaccines, including those delivered through the oral mucosa. 

In spite of the knowledge gained about systemic HIV immunopathogenesis and the genital, rectal, and systemic immune response induced by pathogens or HIV prophylactic vaccines, critical gaps still exist regarding: 1) the oral immunopathogenesis of HIV and AIDS-related oral opportunistic pathogens and 2) the host immune response triggered by these oral pathogens or oral mucosal prophylactic HIV vaccines. These gaps include: initial events of viral entry into target cells of the oral mucosa; oral pathogen transmission locally and systemically; immunopathogenic consequences of oral pathogen translocation to the body; oral pathogen-pathogen interactions, and oral pathogen-host interactions that lead to the development of oral lesions and disease exacerbation; progressive changes in the oral cavity microenvironment (microflora and host factors) upon infection, spread, disease progression, and treatment; events that occur during abortive oral infections; mechanisms of oral immune responses that block HIV and oral opportunistic pathogen infections; cross-talk between oral innate and adaptive immunity that confers protection against HIV and oral pathogens; immune correlates of protection upon oral prophylactic HIV vaccination; the role of soluble saliva and oral mucosal epithelial factors in conferring protective immunity against oral pathogens; and identification and characterization of oral immune networks and their connections with systemic immune networks triggered by oral mucosal prophylactic HIV vaccines or by oral opportunistic pathogens. 

There is a critical group of investigators in the HIV/AIDS field and state-of-the-art technology exists in systems biology and high throughput biological assays to address the overall goal of this initiative. The NIDCR has sponsored a robust basic and translational research portfolio on immunopathogenesis and has seeded efforts in therapeutic and prophylactic strategies. Yet, the gaps described represent roadblocks for the successful development of oral preventive and therapeutic strategies. This initiative will support research that will generate knowledge to provide the basis for the development of oral mucosal prophylactic HIV vaccines and novel, oral therapies against AIDS-related oral opportunistic pathogens.

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This page last updated: February 26, 2014