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 D. Nosanchuk

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 2011

Fingerprint

Chaperonin 60
Histoplasma
Agglutination
Immunoglobulin G
Macrophages
Monoclonal Antibodies
Yeasts
Optical Tweezers
Histoplasmosis
Antibodies
Infection
Immunoglobulins
Epitopes
Microscopy
Flow Cytometry
Light
Antigens
Lung

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Agglutination of Histoplasma capsulatum by IgG monoclonal antibodies against Hsp60 impacts macrophage effector functions. / Guimarães, Allan Jefferson; Frases, Susana; Pontes, Bruno; De Cerqueira, Mariana Duarte; Rodrigues, Marcio L.; Viana, Nathan Bessa; Nimrichter, Leonardo; Nosanchuk, Joshua D.

In: Infection and Immunity, Vol. 79, No. 2, 02.2011, p. 918-927.

Research output: Contribution to journalArticle

Guimarães, AJ, Frases, S, Pontes, B, De Cerqueira, MD, Rodrigues, ML, Viana, NB, Nimrichter, L & Nosanchuk, JD 2011, 'Agglutination of Histoplasma capsulatum by IgG monoclonal antibodies against Hsp60 impacts macrophage effector functions', Infection and Immunity, vol. 79, no. 2, pp. 918-927. https://doi.org/10.1128/IAI.00673-10
Guimarães, Allan Jefferson ; Frases, Susana ; Pontes, Bruno ; De Cerqueira, Mariana Duarte ; Rodrigues, Marcio L. ; Viana, Nathan Bessa ; Nimrichter, Leonardo ; Nosanchuk, Joshua D. / Agglutination of Histoplasma capsulatum by IgG monoclonal antibodies against Hsp60 impacts macrophage effector functions. In: Infection and Immunity. 2011 ; Vol. 79, No. 2. pp. 918-927.
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