TY - JOUR
T1 - Opsonization of Cryptococcus neoformans by human anticryptococcal glucuronoxylomannan antibodies
AU - Zhong, Zhaojing
AU - Pirofski, Liise Anne
PY - 1996
Y1 - 1996
N2 - Cryptococcal meningitis occurs in 6 to 8% of human immunodeficiency virus-infected individuals. Despite the availability of powerful antifungal agents that are active against Cryptococcus neoformans, these drugs generally fail to cure cryptococcal infections in immunocompromised hosts. Alternative approaches to prevention and therapy of cryptococcosis are urgently needed. Complement promotes phagocytosis of C. neoformans, but human antibodies to cryptococcal capsular polysaccharide have not been shown to function as complement-independent opsonins. The goal of our studies was to characterize the in vitro biological function of human antibodies to glucuronoxylomannan (GXM) from individuals immunized with a GXM-tetanus toxoid (GXM-TT) vaccine. We studied sera from nine vaccinees that manifested good serologic responses to GXM-TT. The results indicate that GXM-TT-elicited antibodies promote phagocytosis of C. neoformans by both murine J774 cells and human peripheral blood mononuclear cells (PBMCs). The two sera with the highest titers of anti-GXM immunoglobulin G2 antibodies were the most opsonic. When PBMC FcγRIIa receptors were blocked, a 75% decrease in phagocytosis occurred following incubation of the PBMCs with C. neoformans opsonized with these sera. Our data indicate that, in the absence of complement, human anti-GXM- TT antibodies are opsonic and that antibodies of the immunoglobulin G2 isotype are effective opsonins.
AB - Cryptococcal meningitis occurs in 6 to 8% of human immunodeficiency virus-infected individuals. Despite the availability of powerful antifungal agents that are active against Cryptococcus neoformans, these drugs generally fail to cure cryptococcal infections in immunocompromised hosts. Alternative approaches to prevention and therapy of cryptococcosis are urgently needed. Complement promotes phagocytosis of C. neoformans, but human antibodies to cryptococcal capsular polysaccharide have not been shown to function as complement-independent opsonins. The goal of our studies was to characterize the in vitro biological function of human antibodies to glucuronoxylomannan (GXM) from individuals immunized with a GXM-tetanus toxoid (GXM-TT) vaccine. We studied sera from nine vaccinees that manifested good serologic responses to GXM-TT. The results indicate that GXM-TT-elicited antibodies promote phagocytosis of C. neoformans by both murine J774 cells and human peripheral blood mononuclear cells (PBMCs). The two sera with the highest titers of anti-GXM immunoglobulin G2 antibodies were the most opsonic. When PBMC FcγRIIa receptors were blocked, a 75% decrease in phagocytosis occurred following incubation of the PBMCs with C. neoformans opsonized with these sera. Our data indicate that, in the absence of complement, human anti-GXM- TT antibodies are opsonic and that antibodies of the immunoglobulin G2 isotype are effective opsonins.
UR - http://www.scopus.com/inward/record.url?scp=0029850607&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029850607&partnerID=8YFLogxK
U2 - 10.1128/iai.64.9.3446-3450.1996
DO - 10.1128/iai.64.9.3446-3450.1996
M3 - Article
C2 - 8751883
AN - SCOPUS:0029850607
SN - 0019-9567
VL - 64
SP - 3446
EP - 3450
JO - Infection and immunity
JF - Infection and immunity
IS - 9
ER -