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Traffic of Leukocytes and Cytokine Up-regulation in the Central Nervous System in a Murine Model of Neuroparacoccidioidomycosis

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Abstract

Background

Paracoccidioidomycosis is the most important systemic mycosis in South America. In the last decades, it was observed that central nervous system involvement is frequent, occurring in 12.5 % of the cases. The aim of this study was to report the early inflammatory changes associated with an experimental model of neuroparacoccidioidomycosis (NPCM).

Methods

C57BL/6 mice were infected by intracranial route with 106 yeast cells of PB18 strain of Paracoccidioides brasiliensis. Leukocyte–endothelium interactions were assessed by intravital microscopy 1, 2, 4, and 8 weeks post-infection (p.i.). Chemokine/cytokine levels in the brain and histopathological changes were assessed 4 and 8 weeks p.i..

Results

Intravital microscopy analysis revealed a progressive increase in leukocyte recruitment in the vessels of pia mater with a peak 4 weeks p.i. The chemokine CXCL9 was increased at 4 and 8 weeks p.i., while CCL2, CCL3, and CCL5 were increased at 8 weeks p.i. Histopathological analysis revealed the infiltration of inflammatory cells and the development of progressive granulomatous meningoencephalitis. CCL3 levels correlated with clinical manifestations of disease, as measured by the SHIRPA battery.

Conclusions

The experimental model of NPCM showed increased leukocyte recruitment associated with increased expression of chemokines and nervous tissue inflammation which correlated with clinical manifestations of disease.

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Acknowledgments

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (Fapemig), and Rede Instituto Brasileiro de Neurociência (IBN-Net), Brazil.

Conflict of interest

The authors declare no conflict of interest

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Authors and Affiliations

  1. Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais (UFMG), Av. Antonio Carlos, 6627, Belo Horizonte, Brazil

    Vinicius Sousa Pietra Pedroso, Márcia Carvalho Vilela, Milene Alvarenga Rachid & Antônio Lúcio Teixeira

  2. Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Av. Antonio Carlos, 6627, Belo Horizonte, Brazil

    Patrícia Campi Santos & Patrícia Silva Cisalpino

  3. Laboratório Interdisciplinar de Investigação Médica, Sala 281, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Av. Alfredo Balena, 190. Santa Efigênia, Belo Horizonte, 30130-100, Brazil

    Vinicius Sousa Pietra Pedroso & Antônio Lúcio Teixeira

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  1. Vinicius Sousa Pietra Pedroso
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  2. Márcia Carvalho Vilela
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  3. Patrícia Campi Santos
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  4. Patrícia Silva Cisalpino
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  5. Milene Alvarenga Rachid
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Correspondence to Vinicius Sousa Pietra Pedroso or Antônio Lúcio Teixeira.

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Pedroso, V.S.P., Vilela, M.C., Santos, P.C. et al. Traffic of Leukocytes and Cytokine Up-regulation in the Central Nervous System in a Murine Model of Neuroparacoccidioidomycosis. Mycopathologia 176, 191–199 (2013). https://doi.org/10.1007/s11046-013-9679-3

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  • DOI: https://doi.org/10.1007/s11046-013-9679-3

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