Agglutination of Histoplasma capsulatum by IgG monoclonal antibodies against Hsp60 impacts macrophage effector functions

Allan Jefferson Guimarães, Susana Frases, Bruno Pontes, Mariana Duarte De Cerqueira, Marcio L. Rodrigues, Nathan Bessa Viana, Leonardo Nimrichter, Joshua Daniel Nosanchuk

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Histoplasma capsulatum can efficiently survive within macrophages, facilitating H. capsulatum translocation from the lung into the lymphatics and bloodstream. We have recently generated monoclonal antibodies (MAbs) to an H. 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 agglutination in vitro. In the present study, we characterized the agglutination effects of the antibodies to Hsp60 on H. 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 cause H. 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 agglutinate H. capsulatum significantly impacted pathogenic mechanisms of H. capsulatum during macrophage infection, and the effect was dependent on the antibody subclass and antigen epitope.

Original languageEnglish (US)
Pages (from-to)918-927
Number of pages10
JournalInfection and Immunity
Volume79
Issue number2
DOIs
StatePublished - Feb 1 2011

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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    Guimarães, A. J., Frases, S., Pontes, B., De Cerqueira, M. D., Rodrigues, M. L., Viana, N. B., Nimrichter, L., & Nosanchuk, J. D. (2011). Agglutination of Histoplasma capsulatum by IgG monoclonal antibodies against Hsp60 impacts macrophage effector functions. Infection and Immunity, 79(2), 918-927. https://doi.org/10.1128/IAI.00673-10