9th Conference on Retroviruses and Opportunistic Infections Seattle, Washington - February 24 -February 28, 2002

Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. L2
Melissa Pope
University of Alabama, Birmingham

BACKGROUND: The dendritic cell (DC) system comprises myeloid-derived (MDC) and plasmacytoid-derived (PDC) subsets, that play critical roles in adaptive and innate arms of the immune response. MDCs are found within the epithelia of the body surfaces, blood, lymph, and lymphoid tissues, while PDCs reside in the blood and lymphoid tissues. Being positioned around the body, DCs watch for pathogens, ready to alert the immune system of incoming threats. Thus, a DC encountering an immunodeficiency virus should, in theory, menace the virus, by activating effective anti-viral T and B cell immunity. However, considerable data on MDCs and more recent work on PDCs indicate that DC-entrapped viruses can freely spread between cells and proliferate rapidly particularly when MDCs meet CD4+ T cells, the latter being further augmented when the T cells are activated. Therefore, it seems that immunodeficiency viruses exploit the unique ability of DCs to survey the periphery and capture incoming pathogens, traffic around the body often targeting the lymphoid tissues, and efficiently communicate with naïve and memory T cells. Combined with the fact that at least one subset of MDCs may be the first leukocytes interacting with virus crossing the mucosae, these features provide the basis on which virus maximizes its chance to establish infection even in the face of immune activation. Several molecules including CD4, chemokine receptors, DC-SIGN, and other C-type lectin receptors can contribute to DC-virus interplay, but the involvement of specific receptors likely depends on the DC subsets. How distinct DC subsets and immunodeficiency viruses interact, what cellular and viral factors influence these events, and how this drives virus replication vs stimulation of protective immunity must be delineated.

CONCLUSIONS: Clarifying these issues will define the exact role of DCs in the transmission and dissemination of HIV infection and disease progression. This will facilitate the development of methods to improve the immune-activating capacity of DCs that will advance vaccine and therapeutic approaches as well as the design of strategies to prevent DC-driven infection that may be incorporated in microbicide development.

020224
L2

Copyright © 2002 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.