Antibody-mediated protection against Cryptococcus neoformans pulmonary infection is dependent on B cells.
The pathogenesis of pulmonary Cryptococcus neoformans infection and the efficacy of passive immunoglobulin G1 (IgG1) administration were investigated in B-cell-deficient and C57BL/6J mice. C57BL/6J mice lived longer than B-cell-deficient mice after both intratracheal and intravenous infections. Administration of IgG1 prior to infection prolonged the survival of C57BL/6J mice but had no effect on the survival or numbers of CFU in the lungs of B-cell-deficient mice. C. neoformans infection in B-cell-deficient mice resulted in significantly higher levels of gamma interferon (IFN-gamma), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1alpha (MIP-1alpha) than in C57BL/6J mice. IgG1 administration reduced IFN-gamma and MCP-1 levels in C57BL/6J mice but not in B-cell-deficient mice. In addition, compared to its effect in C57BL/6J mice, C. neoformans infection in FcRgammaIII-deficient, athymic, and SCID mice significantly increased IFN-gamma and MCP-1 levels. IgG1 administration was associated with reduced IFN-gamma levels in C57BL/6J mice but not in FcRgammaIII-deficient, athymic, and SCID mice. These observations suggest that IgG1-mediated protection in this system is a consequence of alterations in the inflammatory response that translate into less damage to the host without directly reducing the fungal burden. For hosts with impaired immunities, the ineffectiveness of passive antibody (Ab) may reflect an inability to down-regulate inflammation and avoid self-damage. The results indicate an important role for B cells in host defense against C. neoformans infection and demonstrate a surprising dependence of Ab-mediated protection on B cells in this system.
Rivera
Johanna
J
Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Zaragoza
Oscar
O
Casadevall
Arturo
A
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D003453:Cryptococcosis / Q000276:immunology*; D003455:Cryptococcus neoformans / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D005434:Flow Cytometry; D007116:Immunization, Passive; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000166:cytology / Q000382:microbiology; D051379:Mice; D013534:Survival
D000906:Antibodies; D016207:Cytokines; D007073:Immunoglobulin E