Effect of serum IgG1 to Cryptococcus neoformans glucuronoxylomannan on murine pulmonary infection.
Little is known about the role of Ab in protection against pulmonary fungal pathogens. The ability of murine IgG1 mAb 2H1 to modify pulmonary Cryptococcus neoformans infection was investigated in intratracheal infection. mAb 2H1 binds C. neoformans glucuronoxylomannan. mAb 2H1 was given to A/JCr mice 24 h before infection. Two C. neoformans strains were studied: ATCC 24067 (serotype D) and 62070 (serotype A). Fungal burden was determined by CFU 14 days after infection for both strains, and at 2 h, 24 h, 48 h, 7 days, and 28 days after infection for strain 24067. On day 14, mAb 2H1 treatment reduced CFU in the lung, brain, and liver for strain 62070 infection. Minor reductions in lung CFU followed infection with strain 24067 in mAb 2H1-treated mice, despite prolonged survival. The limited ability of mAb 2H1 to reduce lung CFU may reflect rapid phagocytosis of yeast by alveolar macrophages, seen by electron microscopy 2 h after infection, regardless of whether mice had received mAb. Alveolar macrophages phagocytosed and reduced C. neoformans CFU in vitro only in the presence of mAb 2H1. Differences were apparent in phagocytosis and in vitro killing between strains 24067 and 62070. Serum IgG1 modified the course of pulmonary infection in mice by prolonging survival, reducing CFU, and reducing tissue glucuronoxylomannan Ag. mAb administration was associated with enhanced granulomatous inflammation, but did not prevent infection or dissemination. Despite incomplete protection by serum Ab against pulmonary infection, our results provide encouragement for continued vaccine development.
Feldmesser
M
M
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Casadevall
A
A
D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology*; D003453:Cryptococcosis / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D007150:Immunohistochemistry; D008171:Lung Diseases / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008805:Mice, Inbred A; D011134:Polysaccharides / Q000276:immunology*
D000908:Antibodies, Fungal; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011134:Polysaccharides; C027478:glucuronoxylomannan