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

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 struct...

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Bibliographic Details
Published in:Brazilian journal of microbiology 2021-06, Vol.52 (2), p.479-489
Main Authors: dos Santos, Giulia Maria Pires, dos Santos, Gustavo Ramalho Cardoso, Xisto, Mariana Ingrid Dutra da Silva, Rollin-Pinheiro, Rodrigo, Baptista, Andréa Regina de Souza, da Rocha, Elisabeth Martins da Silva, Machado, Ricardo Luiz Dantas, Barreto-Bergter, Eliana, Pinto, Marcia Ribeiro
Format: Article
Language:English
Subjects:
Animals
Antigenicity
Antigens
Bacterial and Fungal Pathogenesis - Research Paper
Biomedical and Life Sciences
Carbohydrates
Cell activation
Cell Wall - chemistry
Cell Wall - immunology
Cell walls
Chains
Chiroptera - microbiology
Endopeptidase K
Enzyme-linked immunosorbent assay
Female
Food Microbiology
Galactose - analogs & derivatives
Gas chromatography
Glycopeptides - chemistry
Glycopeptides - pharmacology
Histoplasma - chemistry
Histoplasma - immunology
Histoplasma - isolation & purification
Histoplasma capsulatum
Histoplasmosis
Histoplasmosis - genetics
Histoplasmosis - immunology
Histoplasmosis - microbiology
Humans
Immune response
Immune system
Immunogenicity
Interferon-gamma - genetics
Interferon-gamma - immunology
Interleukin 10
Interleukin-10 - genetics
Interleukin-10 - immunology
Life Sciences
Macrophages
Macrophages, Peritoneal - drug effects
Macrophages, Peritoneal - immunology
Male
Mannans - chemistry
Mannans - pharmacology
Mass Spectrometry
Medical Microbiology
Methylation
Mice
Mice, Inbred C57BL
Microbial Ecology
Microbial Genetics and Genomics
Microbiology
Morbidity
Mycology
NMR
Nuclear magnetic resonance
Oxidation
Peritoneum
Phagocytosis
Phagocytosis - drug effects
Proteinase
Rabbits
Reactivity
Structural analysis
Two dimensional analysis
Yeast
Yeasts
γ-Interferon
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Summary: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 -Man p (1 → 6) residues substituted at O -2 by α- d -Man p (1 → 2)–linked side chains, non-reducing end units of α- d -Gal f , or β- d -Gal p linked (1→ 6) to α- d -Man p 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.
ISSN:1517-8382
1678-4405
DOI:10.1007/s42770-021-00447-w