Objective: To determine the contribution of anti-glucuronoxylomannan monoclonal antibody (MAb18B7) to the fungicidal capacity of polymorphonuclear leukocytes (PMNL) from HIV-infected patients towards Cryptococcus neoformans.
Design: Killing activity and superoxide anion generation were evaluated in the presence or absence of MAb18B7 in an in vitro system.
Methods: Killing activity was determined by colony forming unit inhibition assay. Superoxide generation was measured in the presence or absence of zymosan, C. neoformans, or Candida albicans. CD16, CD32, and CD64 molecules on PMNL were evaluated by cytofluorometric analysis.
Results: MAb18B7 strongly influenced the phagocytic and killing activities against encapsulated C. neoformans and consistently enhanced superoxide anion generation. Expression of CD16, and to a lesser extent CD64, on PMNL was required for MAb18B7-induced superoxide generation. By blocking CD16 and CD64 molecules with anti-CD16 and anti-CD64 MAb, a significant down-regulation of MAb18B7-induced fungicidal activity was observed.
Conclusions: Our results demonstrate that MAb18B7 selectively enhances the killing mechanisms of PMNL from HIV-infected patients against encapsulated C. neoformans. The availability of CD16 and CD64 molecules on PMNL plays a critical role.