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Peptidogalactomannan from Histoplasma capsulatum yeast cell wall: role of the chemical structure in recognition and activation by peritoneal macrophages

  • Bacterial and Fungal Pathogenesis - Research Paper
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Abstract

Histoplasma capsulatum is the causative agent of histoplasmosis, a systemic disease responsible for most reported causes of morbidity and mortality among immunosuppressed individuals. Peptidogalactomannan (pGM) was purified from the yeast cell wall of H. capsulatum isolated from bats, and its structure and involvement in modulating the host immune response were evaluated. Gas chromatography, methylation analysis, and two-dimensional nuclear magnetic resonance (2D-NMR) were used for the structural characterization of pGM. Methylation and 2D-NMR data revealed that pGM comprises a main chain containing α-d-Manp (1 → 6) residues substituted at O-2 by α-d-Manp (1 → 2)–linked side chains, non-reducing end units of α-d-Galf, or β-d-Galp linked (1→ 6) to α-d-Manp side chains. The involvement of H. capsulatum pGM in antigenic reactivity and in interactions with macrophages was demonstrated by ELISA and phagocytosis assay, respectively. The importance of the carbohydrate and protein moieties of pGM in sera reactivity was evaluated. Periodate oxidation abolished much pGM antigenic reactivity, suggesting that the sugar moiety is the most immunogenic part of pGM. Reactivity slightly decreased in pGM treated with proteinase K, suggesting that the peptide moiety plays a minor role in pGM antigenicity. In vitro experiments suggested that pGM is involved in the phagocytosis of H. capsulatum yeast and induction of IL-10 and IFN-γ secretion by peritoneal macrophages from C57BL/6 mice. These findings demonstrated the role of pGM in the H. capsulatum-host interaction.

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Acknowledgments

We thank Paulo A. S. Mourão for the advice, encouragement, and support of this manuscript. We also thank Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-Financial Code 001, Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq), and Universidade Federal Fluminense (UFF).

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Funding

This study was funded by Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ) (grant number E-26/200.577/2016). This study was partly funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (Financial Code 001) and Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq).

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Authors and Affiliations

  1. Instituto Biomédico, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense UFF, Rua Prof. Hernani Melo, 101, 3° andar, sala 303, Niterói, Brazil

    Giulia Maria Pires dos Santos, Andréa Regina de Souza Baptista, Elisabeth Martins da Silva da Rocha, Ricardo Luiz Dantas Machado & Marcia Ribeiro Pinto

  2. Instituto de Bioquímica Médica, Programa de Glicobiologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Gustavo Ramalho Cardoso dos Santos

  3. Instituto de Microbiologia Paulo de Góes, Departamento de Microbiologia Geral, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Mariana Ingrid Dutra da Silva Xisto, Rodrigo Rollin-Pinheiro & Eliana Barreto-Bergter

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  1. Giulia Maria Pires dos Santos
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  2. Gustavo Ramalho Cardoso dos Santos
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Contributions

GMPS, MIDSX, RR-P, and MRP designed the experiments and drafted the manuscript. GMPS, GRCS, MIDSX, and RR-P performed all experiments. GMPS, GRCS, MIDSX, RR-P, ARSB, EMSR, RLDM, EB-B, and MRP analyzed the data. EB-B critically revised the manuscript. All authors read and approved the manuscript.

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Correspondence to Marcia Ribeiro Pinto.

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This study was approved by the research ethics committee of Instituto Nacional de Infectologia Evandro Chagas, Fiocruz, accession number 19109913.0.0000.5262, and by the Institutional Animal Welfare Committee of the Universidade Federal Fluminense (UFF), accession code 731/2016/CEUA-UFF.

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dos Santos, G.M.P., dos Santos, G.R.C., Xisto, M.I.D.d. et al. Peptidogalactomannan from Histoplasma capsulatum yeast cell wall: role of the chemical structure in recognition and activation by peritoneal macrophages. Braz J Microbiol 52, 479–489 (2021). https://doi.org/10.1007/s42770-021-00447-w

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