Opsonization of Cryptococcus neoformans by human anticryptococcal glucuronoxylomannan antibodies

Zhaojing Zhong, Liise-anne Pirofski

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3446-3450
Number of pages5
JournalInfection and Immunity
Volume64
Issue number9
StatePublished - 1996

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Cryptococcus neoformans
Antibodies
Phagocytosis
Opsonin Proteins
Blood Cells
Tetanus Toxoid
Serum
Cryptococcal Meningitis
Cryptococcosis
Immunoglobulin Isotypes
Antifungal Agents
Immunocompromised Host
glucuronoxylomannan
Immunoglobulins
HIV
Infection
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Immunology

Cite this

Opsonization of Cryptococcus neoformans by human anticryptococcal glucuronoxylomannan antibodies. / Zhong, Zhaojing; Pirofski, Liise-anne.

In: Infection and Immunity, Vol. 64, No. 9, 1996, p. 3446-3450.

Research output: Contribution to journalArticle

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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.

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