Antibody binding alters the characteristics and contents of extracellular vesicles released by Histoplasma capsulatum

Ludmila Matos Baltazar, Ernesto S. Nakayasu, Tiago J.P. Sobreir, Hyungwon Choi, Arturo Casadevall, Leonardo Nimrichter, Joshua D. Nosanchuk

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Histoplasma capsulatum produces extracellular vesicles containing virulence-associated molecules capable of modulating host machinery, benefiting the pathogen. Treatment of H. capsulatum cells with monoclonal antibodies (MAbs) can change the outcome of infection in mice. We evaluated the sizes, enzymatic contents, and proteomic profiles of the vesicles released by fungal cells treated with either protective MAb 6B7 (IgG1) or nonprotective MAb 7B6 (IgG2b), both of which bind H. capsulatum heat shock protein 60 (Hsp60). Our results showed that treatment with either MAb was associated with changes in size and vesicle loading. MAb treatments reduced vesicle phosphatase and catalase activities compared to those of vesicles from untreated controls. We identified 1,125 proteins in vesicles, and 250 of these manifested differences in abundance relative to that of proteins in vesicles isolated from yeast cells exposed to Hsp60-binding MAbs, indicating that surface binding of fungal cells by MAbs modified protein loading in the vesicles. The abundance of upregulated proteins in vesicles upon MAb 7B6 treatment was 44.8% of the protein quantities in vesicles from fungal cells treated with MAb 6B7. Analysis of orthologous proteins previously identified in vesicles from other fungi showed that different ascomycete fungi have similar proteins in their extracellular milieu, many of which are associated with virulence. Our results demonstrate that antibody binding can modulate fungal cell responses, resulting in differential loading of vesicles, which could alter fungal cell susceptibility to host defenses. This finding provides additional evidence that antibody binding modulates microbial physiology and suggests a new function for specific immunoglobulins through alterations of fungal secretion.

Original languageEnglish (US)
Article numbere00085-15
JournalmSphere
Volume1
Issue number2
DOIs
StatePublished - Mar 1 2016

Fingerprint

Histoplasma
Antibodies
Proteins
Chaperonin 60
Monoclonal Antibodies
Virulence
Fungi
Ascomycota
Extracellular Vesicles
Phosphoric Monoester Hydrolases
Protein Binding
Proteomics
Catalase
Immunoglobulins
Immunoglobulin G
Yeasts
Infection

Keywords

  • H. capsulatum
  • Hsp60
  • Monoclonal antibodies
  • Vesicles

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Baltazar, L. M., Nakayasu, E. S., Sobreir, T. J. P., Choi, H., Casadevall, A., Nimrichter, L., & Nosanchuk, J. D. (2016). Antibody binding alters the characteristics and contents of extracellular vesicles released by Histoplasma capsulatum. mSphere, 1(2), [e00085-15]. https://doi.org/10.1128/mSphere.00085-15

Antibody binding alters the characteristics and contents of extracellular vesicles released by Histoplasma capsulatum. / Baltazar, Ludmila Matos; Nakayasu, Ernesto S.; Sobreir, Tiago J.P.; Choi, Hyungwon; Casadevall, Arturo; Nimrichter, Leonardo; Nosanchuk, Joshua D.

In: mSphere, Vol. 1, No. 2, e00085-15, 01.03.2016.

Research output: Contribution to journalArticle

Baltazar LM, Nakayasu ES, Sobreir TJP, Choi H, Casadevall A, Nimrichter L et al. Antibody binding alters the characteristics and contents of extracellular vesicles released by Histoplasma capsulatum. mSphere. 2016 Mar 1;1(2). e00085-15. https://doi.org/10.1128/mSphere.00085-15
Baltazar, Ludmila Matos ; Nakayasu, Ernesto S. ; Sobreir, Tiago J.P. ; Choi, Hyungwon ; Casadevall, Arturo ; Nimrichter, Leonardo ; Nosanchuk, Joshua D. / Antibody binding alters the characteristics and contents of extracellular vesicles released by Histoplasma capsulatum. In: mSphere. 2016 ; Vol. 1, No. 2.
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