Mucosal Immune System and HIV/SIV.

Abstract

Current epidemiological data convincingly indicate that HIV infection is acquired predominantly by the mucosal route, analogous with the majority of infectious diseases [1]. Mucosal surfaces of the genital and intestinal tracts are the major sites of virus entry, yet major discoveries and advances in the technologies in the last decade alone have reinforced the importance of examining mucosal immune responses. The earliest and most profound alterations of the immune system occur in mucosal tissues of the intestinal tract, which constitute a crucial step in the pathogenesis of HIV [2, 3]. Furthermore, untreated HIV patients are also usually infected by opportunistic mucosal pathogens of viral, bacterial, fungal and parasitic origin. The marked quantitative and qualitative differences of the mucosal and systemic compartments of the immune system comprise the dominant mucosal site of exposure to environmental antigens; phenotypically distinct cell populations including the antigen-presenting dendritic cells, macrophages, epithelial cells, T and B lymphocytes, innate lymphoid cells, plasma cells; production and selective transport of antibodies; and unique innate factors of immunity present in mucosal tissues and secretions. In particular, HIV exploits the unique aspects of the mucosal immune system, especially its reservoir of activated CD4+ T target cells, which support viral infection, amplification, mutation, and destruction of key immunoregulatory cells involved in mucosal immunity. Loss of mucosal barrier integrity permits translocation of foreign antigens into the systemic circulation resulting in further viral replication and continual seeding of viral reservoirs [3, 4]. Furthermore, the loss of immunoregulatory T cells in mucosal tissues contributes to the lack of normal immune suppression, leading to increased levels of inflammation supportive of continued HIV replication and persistence in tissues. Finally, mucosal tissues are increasingly recognized as the major reservoir for viral persistence in patients on antiretroviral therapy, especially in the Gut-Associated Lymphoid Tissues (GALT) of the lower intestinal tract.