Salivary and mucosal immune responses to HIV and its co-pathogens

The profound effects that HIV induces in systemic immunity have been well characterised, but the situation with regard to mucosal immune responses is less clear. Oral cavity fluids have been used as a marker of the mucosal immune system. Whole and parotid saliva IgA, IgA1 and IgA2 concentrations have been found to be lower in both HIV infection and AIDS subjects, whereas serum IgA and IgA subclasses are markedly raised, suggesting a dichotomy between systemic and secretory immunity. Salivary antibodies to HIV can be readily detected and secretory IgA antibody can be neutralising to some strains of HIV. HIV vaccines can also induce antibody responses in saliva, but vaccination routes other than parenteral immunisation are needed. Antibody responses to oral microbes have also been studied and it has been shown that IgA, IgA1 and IgA2 subclass antibody titres to Candida albicans and to Streptococcus mutans are increased in whole or parotid saliva from HIV patients, but reduced in AIDS patients, suggesting a compensatory response which is overcome with progressive immunodeficiency. The avidity of salivary IgA antibodies to Candida in HIV seems unimpaired, whereas relative avidities of serum antibodies in HIV patients with candidiasis are lowered. Non-specific factors which may inhibit Candida and other opportunist pathogens are also found in saliva. The candidacidal, myelomonocytic protein calprotectin is present in saliva at levels which are biologically active, although levels are lowered in HIV infection. Overall, HIV infection appears to be associated with disregulation of a number of immune factors at the mucosal surface, but the ability of patients with HIV infection to mount specific antibody secretory responses seems to be relatively intact until late in infection.