Oral mucosal immunity and HIV infection: current status.

There is a paradox that profound HIV-induced immunodeficiency is present systemically, whereas the majority of infections associated with HIV disease are present or initiated at mucosal surfaces. There is therefore a need to understand both specific and non-specific mechanisms of mucosal protection against HIV and its copathogens. The majority of HIV infections occur as a result of the passage of virus across mucosal membranes. Resistance to HIV infection at mucosal surfaces may be related to HIV-specific CD8+ T cell responses in some individuals and may be the basis for protective vaccine design. However, T-cells, macrophages and dendritic cells in mucosa may be a portal of entry for HIV. Transcytosis of HIV can occur from the mucosal to the submucosal surface and vice versa, and may be inhibited by mucosal immunoglobulins and neutralizing IgA within epithelial cells. HIV-induced alterations to oral epithelial cells, together with impairment of mucosal CD4+ T-cells and consequent altered cytokine secretion, may contribute to secondary infections. It also appears that HIV infection is associated with decreased salivary IgA levels, although a dichotomy between IgA concentrations in saliva and serum has been reported. Mucosal antibody responses, however, seem to be maintained. Considerable attention has been given to the possibility of mucosal immunization against HIV and there is evidence that secretory IgA antibody is neutralizing to different HIV strains. In addition to specific immune factors, it is likely that innate nonspecific factors may be significant in protecting mucosal surfaces, including lactoferrin, secretory leukocyte protease inhibitor, mucins, proline rich proteins and cystatins. These may be useful candidate virucides in topical preparations. Thus humoral, cellular and innate immune mechanisms, as well as lymphocyte-epithelial interactions, may all be impaired at mucosal surfaces as a result of HIV infection and may contribute to the susceptibility of mucosa to infective processes.