An anti-beta-glucan monoclonal antibody inhibits growth and capsule formation of Cryptococcus neoformans in vitro and exerts therapeutic, anticryptococcal activity in vivo.
In this study we tested the in vitro and in vivo anti-Cryptococcus neoformans activity of an antilaminarin (anti-beta-glucan) monoclonal antibody (MAb 2G8) (immunoglobulin G2b) which was previously shown to inhibit the growth of beta-glucan-exposing Candida albicans cells. Here we show that MAb 2G8 binds to the cell wall of C. neoformans and inhibits its growth to an extent comparable to that observed for C. albicans. Binding and growth inhibition were detected almost equally for encapsulated and acapsular C. neoformans strains. In addition, at subinhibitory concentrations, MAb 2G8 reduced the capsule thickness without affecting protease or phospholipase production. Acapsular fungal cells, but not encapsulated fungal cells, were opsonized by the antibody and more efficiently phagocytosed and killed by human monocytes and by murine peritoneal macrophages. A single administration of MAb 2G8 resulted in a reduction in the fungal burden in the brains and livers of mice systemically infected with a highly virulent, encapsulated C. neoformans strain. This protective effect was also detected in neutropenic mice. Overall, these findings demonstrate that cell wall beta-glucan of encapsulated C. neoformans is accessible to antibodies which can exert remarkable anticryptococcal activities in vitro and in vivo.
Rachini
Anna
A
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06126 Perugia, Italy.
Pietrella
Donatella
D
Lupo
Patrizia
P
Torosantucci
Antonella
A
Chiani
Paola
P
Bromuro
Carla
C
Proietti
Carla
C
Bistoni
Francesco
F
Cassone
Antonio
A
Vecchiarelli
Anna
A
D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D001921:Brain / Q000382:microbiology; D002473:Cell Wall / Q000276:immunology*; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D003453:Cryptococcosis / Q000276:immunology* / Q000628:therapy; D003455:Cryptococcus neoformans / Q000254:growth & development* / Q000276:immunology*; D005260:Female; D005936:Glucans; D006801:Humans; D007167:Immunotherapy; D008099:Liver / Q000382:microbiology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology; D010587:Phagocytosis; D011134:Polysaccharides / Q000276:immunology*; D011485:Protein Binding; D047071:beta-Glucans / Q000276:immunology
D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D005936:Glucans; D011134:Polysaccharides; D047071:beta-Glucans; C008247:laminaran