Open AccessAgglutination of Histoplasma capsulatum by IgG Monoclonal Antibodies against Hsp60 Impacts Macrophage Effector Functions
Author(s) -
Allan J. Guimarães,
Susana Frasés,
Bruno Pontes,
Mariana Duarte de Cerqueira,
Márcio L. Rodrigues,
Nathan B. Viana,
Leonardo Nimrichter,
Joshua D. Nosanchuk
Publication year - 2011
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00673-10
Subject(s) - biology , monoclonal antibody , histoplasma capsulatum , microbiology and biotechnology , effector , immunology , agglutination (biology) , antibody , histoplasma , macrophage , virology , histoplasmosis , biochemistry , in vitro
Histoplasma capsulatum can efficiently survive within macrophages, facilitatingH. capsulatum translocation from the lung into the lymphatics and bloodstream. We have recently generated monoclonal antibodies (MAbs) to anH. capsulatum surface-expressed heat shock protein of 60 kDa (Hsp60) that modify disease in a murine histoplasmosis model. Interestingly, the MAbs induced different degrees of yeast cell agglutinationin vitro . In the present study, we characterized the agglutination effects of the antibodies to Hsp60 onH. capsulatum yeast cells by light microscopy, flow cytometry, dynamic light scattering, measuring zeta potential, and using optical tweezers. We found that immunoglobulin Gs (IgGs) to Hsp60 causeH. capsulatum aggregation dependent on the (i) concentration of MAbs, (ii) MAb binding constant, and (iii) IgG subclass. Furthermore, infection of macrophages using agglutinates of various sizes after incubation with different Hsp60-binding MAbs induced association to macrophages through distinct cellular receptors and differentially affected macrophage antifungal functions. Hence, the capacity of IgG MAbs to agglutinateH. capsulatum significantly impacted pathogenic mechanisms ofH. capsulatum during macrophage infection, and the effect was dependent on the antibody subclass and antigen epitope.