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Glycolipid Sensing and Innate Immunity in Paracoccidioidomycosis

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Abstract

Distinct glycolipid profiles are described in microorganisms, which have been shown to modulate the innate immune system. We tested the hypothesis that glycosphingolipids from Paracoccidioides brasiliensis have immunomodulatory properties on monocytes and dendritic cells of two groups of healthy individuals, one cured of paracoccidioidomycosis in the past (CUR-I) and the other nonexposed to P. brasiliensis (HNE-I). Two classes of glycosphingolipids purified from yeast cells were evaluated: a neutral glycosphingolipid, monohexosylceramide (CMH), and acidic glycosylinositolphosphorylceramides (GIPCs). Both glycosphingolipids affected the functioning of innate immunity cells, interfering with the antigen presenting process: P. brasiliensis yeast cells phagocytosis, IL-10 secretion, and costimulatory molecules and recognition receptors expression by monocytes were altered, while dendritic cell antigen presentation to autologous T cells was markedly down-modulated as shown by reduced T-cell proliferative responses. The mechanisms by which CMH and GIPCs exert their effects differ since the target cells did not always respond similarly to the challenge with the glycosphingolipids. Moreover, CUR-I and HNE-I presented different responses to the glycosphingolipids. Differences not only in the glycosphingolipid structure (such as the polar head group or the ceramide moiety), but also in the innate immunity properties of CUR-I and HNE-I, may underlie these differences and contribute to individual’s susceptibility or resistance to develop paracoccidioidomycosis.

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Acknowledgments

This work was supported by grants from Fapesp #07/58598-8 (GB) and 07/58462-9 (VGB) and from CNPq (AS, MJSM, HT, AJSD, and GB).

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Authors and Affiliations

  1. Laboratory of Medical Investigation Unit 56, Division of Clinical Dermatology, Medical School, University of São Paulo, Av Dr. Eneas de Carvalho Aguiar 470, São Paulo, CEP 05403-000, Brazil

    Vanessa G. Batista, Alberto J. S. Duarte & Gil Benard

  2. Division of Glycoconjugate Immunochemistry, Department of Biochemistry, São Paulo Medical School, Federal University of São Paulo, São Paulo, Brazil

    Marcos S. Toledo, Anita H. Straus & Helio K. Takahashi

  3. Department of Clinical Analyses, Faculty of Pharmaceutical Sciences, UNESP, Araraquara, Brazil

    Maria J. S. Mendes-Giannini

  4. Laboratory of Medical Investigation Unit 53, Tropical Medicine Institute, University of São Paulo, São Paulo, Brazil

    Gil Benard

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  1. Vanessa G. Batista
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  6. Helio K. Takahashi
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  7. Gil Benard
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Correspondence to Gil Benard.

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Batista, V.G., Toledo, M.S., Straus, A.H. et al. Glycolipid Sensing and Innate Immunity in Paracoccidioidomycosis. Mycopathologia 178, 153–162 (2014). https://doi.org/10.1007/s11046-014-9783-z

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  • DOI: https://doi.org/10.1007/s11046-014-9783-z

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