Normalization of anti-cryptococcal activity and interleukin-12 production after highly active antiretroviral therapy

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Abstract
To investigate the effect of highly active antiretroviral treatment (HAART) on antifungal and secretory functions of polymorphonuclear leukocytes (PMNL) from HIV-infected patients with high viral load. Antifungal activity, oxygen-dependent mechanisms and interleukin (IL)-12 secretion were evaluated in PMNL from HIV-infected patients before and 3 months after commencing HAART. PMNL antifungal activity was evaluated by effects on fungal colony-forming units. Superoxide anion (O2−) production was determined by superoxide dismutase reduction and IL-12 was determined by enzyme-linked immunosorbent assay in supernatant fluids of PMNL cultured for 18 h. PMNL from HIV-infected patients showed dysregulation of antimicrobial and secretory functions. A selective defect in antimicrobial activity against encapsulated Cryptococcus neoformans correlated with baseline O2−overproduction, which drastically decreased upon microbial stimulation. Similarly, constitutive secretion of IL-12 was blocked by exposure to microbial products. PMNL analysed after 3 months of HAART showed restoration of antimicrobial activity against encapsulated C. neoformans, reduction in O2−formation by unstimulated cells and restoration of oxidative burst after appropriate stimulation, and reduction of IL-12 hypersecretion. PMNL from HIV-infected patients with high viral load have impaired function; HAART normalizes antimicrobial and secretory activities. The effects of HAART on innate immunity provide new prospects for reduction of HAART-mediated opportunistic infections.

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