TY - JOUR
T1 - Antifungal activity of a human antiglucuronoxylomannan antibody
AU - Zhong, Zhaojing
AU - Pirofski, Liise Anne
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1998
Y1 - 1998
N2 - The human immunoglobulin M (IgM) monoclonal antibody (MAb) 2E9 binds the glucuronoxylomannan (GXM) of Cryptococcus neoformans serotypes A, B, and D. This study was undertaken to determine the opsonic efficacy of 2E9 and its ability to promote the antifungal activity of human polymorphonuclear neutrophils (PMNs) against C. neoformans. We incubated purified PMNs with fluorescein isothiocyanate-labeled C. neoformans cells that were treated with the GXM IgM 2E9, IgM antibodies that do not bind GXM, and rabbit and human factor-B-deficient serum as complement sources. PMN-associated C. neoformans cells fluoresced and were detected with a fluorescence-activated cell sorter. The amount of phagocytosis was defined as the percent fluorescing PMNs, which was 37% for yeast cells opsonized with 2E9 plus rabbit serum and 57% for yeast cells opsonized with 2E9 plus factor-B-deficient serum. Phagocytosis was significantly greater for yeast cells that were treated with 2E9 plus a complement source than for yeast cells treated with the complement sources alone or treated with the control IgMs alone or with the complement sources. Fluorescence quenching and light and electron microscopy of the phagocytosis mixtures revealed that 2E9-opsonized yeast cells were internalized by PMNs. Maximal inhibition of C. neoformans growth occurred when PMNs were cocultured with yeast cells that were opsonized with 2E9 plus a complement source. Our data demonstrate that the human GXM IgM 2E9 can mediate PMN phagocytosis and C. neoformans growth inhibition in vitro. These findings strongly suggest that antibody-mediated deposition of complement components on the cryptococcal capsule can augment PMN complement receptor-mediated antifungal activity. Antibody activation of complement-mediated effector cell antifungal mechanisms may play a role in host defense against cryptococcosis and represents a goal for the use of MAbs to treat or prevent human C. neoformans infections.
AB - The human immunoglobulin M (IgM) monoclonal antibody (MAb) 2E9 binds the glucuronoxylomannan (GXM) of Cryptococcus neoformans serotypes A, B, and D. This study was undertaken to determine the opsonic efficacy of 2E9 and its ability to promote the antifungal activity of human polymorphonuclear neutrophils (PMNs) against C. neoformans. We incubated purified PMNs with fluorescein isothiocyanate-labeled C. neoformans cells that were treated with the GXM IgM 2E9, IgM antibodies that do not bind GXM, and rabbit and human factor-B-deficient serum as complement sources. PMN-associated C. neoformans cells fluoresced and were detected with a fluorescence-activated cell sorter. The amount of phagocytosis was defined as the percent fluorescing PMNs, which was 37% for yeast cells opsonized with 2E9 plus rabbit serum and 57% for yeast cells opsonized with 2E9 plus factor-B-deficient serum. Phagocytosis was significantly greater for yeast cells that were treated with 2E9 plus a complement source than for yeast cells treated with the complement sources alone or treated with the control IgMs alone or with the complement sources. Fluorescence quenching and light and electron microscopy of the phagocytosis mixtures revealed that 2E9-opsonized yeast cells were internalized by PMNs. Maximal inhibition of C. neoformans growth occurred when PMNs were cocultured with yeast cells that were opsonized with 2E9 plus a complement source. Our data demonstrate that the human GXM IgM 2E9 can mediate PMN phagocytosis and C. neoformans growth inhibition in vitro. These findings strongly suggest that antibody-mediated deposition of complement components on the cryptococcal capsule can augment PMN complement receptor-mediated antifungal activity. Antibody activation of complement-mediated effector cell antifungal mechanisms may play a role in host defense against cryptococcosis and represents a goal for the use of MAbs to treat or prevent human C. neoformans infections.
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U2 - 10.1128/cdli.5.1.58-64.1998
DO - 10.1128/cdli.5.1.58-64.1998
M3 - Article
C2 - 9455881
AN - SCOPUS:0031907654
VL - 5
SP - 58
EP - 64
JO - Clinical and Diagnostic Laboratory Immunology
JF - Clinical and Diagnostic Laboratory Immunology
SN - 1071-412X
IS - 1
ER -