Infectious Diseases And Immunity Branch
Division Of Basic And Translational Sciences
Objective:
This initiative seeks to define the innate factors of the oral mucosal immune system involved in the resistance to the acquisition and spread of HIV and associated opportunistic infections.
In response to the AIDS pandemic, the NIDCR is committed to a comprehensive biomedical and behavioral research program to better understand the basic biology of HIV infection, develop effective therapies to treat it and the associated health complications, and design interventions to prevent new infections from occurring.
Recent epidemiological evidence indicates that exogenous infection with HIV, which could occur during receptive oral sex, is an extremely rare event. This is remarkable in that exposure of other mucosal surfaces such as anal and vaginal tissues to infectious HIV virions results in infection. The resistance to oral infection occurs in seronegative individuals indicating that previous exposure to HIV is not necessary for protection. Thus, antibodies and cell mediated immunity appear to be less important than innate immunity in protecting humans from oral infection.
To study this further, the NIDCR will encourage research on the innate factors in the oral cavity that might prevent HIV infection. These would include salivary mucins, histatins, hypotonicity, cytokines/chemokines, beta-defensins, host inflammatory responses and antiviral factors produced by epithelial cells and leukocytes.
The field of innate immunity is very active right now and we are developing a clearer picture of how the host defends itself from infectious microbes. This is a rapidly growing area and the major factors appear to be cytokines, Toll-like receptors, mammalian signaling pathways, host defense antimicrobial peptides, leukocyte-derived agents, and heat shock proteins. NIDCR is currently supporting research on these topics and is well poised to move forward on this initiative. A better understanding of innate factors that control oral HIV infection can suggest novel microbicides and targets for enhanced resistance to mucosal infection. This initiative will likely employ a RFA for R01, R21 and R03 grant applications.
This initiative meets the tentative research agenda outlined by the NIH Office of AIDS Research for FY2004.