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Antibody to capsular polysaccharide enhances the function of neutrophils from patients with AIDS against Cryptococcus
C Monari1, A Casadevall, C Retini
1Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
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.
Insights
The anti-glucuronoxylomannan monoclonal antibody (MAb18B7) enhances polymorphonuclear leukocyte (PMNL) killing of Cryptococcus neoformans in HIV patients. This enhancement relies on CD16 and CD64 molecules on PMNL.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- HIV infection impairs immune function, increasing susceptibility to opportunistic infections like Cryptococcus neoformans.
- Polymorphonuclear leukocytes (PMNL) are crucial for fighting fungal infections, but their capacity can be compromised in HIV patients.
- Cryptococcus neoformans poses a significant threat, particularly to individuals with weakened immune systems.
Purpose of the Study:
- To investigate the role of anti-glucuronoxylomannan monoclonal antibody (MAb18B7) in augmenting the fungicidal activity of PMNL against Cryptococcus neoformans in HIV-infected individuals.
- To elucidate the mechanisms by which MAb18B7 influences PMNL function, specifically superoxide anion generation and killing capacity.
Main Methods:
- An in vitro system was employed to assess PMNL killing activity and superoxide anion generation in the presence and absence of MAb18B7.
- Colony forming unit inhibition assays were used to quantify fungal killing.
- Cytofluorometric analysis evaluated the expression of CD16, CD32, and CD64 molecules on PMNL.
Main Results:
- MAb18B7 significantly enhanced the phagocytic and fungicidal activities of PMNL against encapsulated Cryptococcus neoformans.
- Superoxide anion generation by PMNL was consistently increased by MAb18B7.
- The MAb18B7-mediated enhancement of superoxide generation was dependent on the expression of CD16 and CD64 molecules on PMNL.
Conclusions:
- MAb18B7 selectively boosts the fungicidal mechanisms of PMNL in HIV-infected patients against encapsulated Cryptococcus neoformans.
- The presence and availability of CD16 and CD64 molecules on PMNL are critical for MAb18B7's effectiveness.
- These findings suggest a potential therapeutic role for MAb18B7 in managing Cryptococcus neoformans infections in immunocompromised individuals.