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The role of the P2X7 receptor in murine cutaneous leishmaniasis: aspects of inflammation and parasite control

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Abstract

Leishmania amazonensis is the etiological agent of diffuse cutaneous leishmaniasis. The immunopathology of leishmaniasis caused by L. amazonensis infection is dependent on the pathogenic role of effector CD4+ T cells. Purinergic signalling has been implicated in resistance to infection by different intracellular parasites. In this study, we evaluated the role of the P2X7 receptor in modulating the immune response and susceptibility to infection by L. amazonensis. We found that P2X7-deficient mice are more susceptible to L. amazonensis infection than wild-type (WT) mice. P2X7 deletion resulted in increased lesion size and parasite load. Our histological analysis showed an increase in cell infiltration in infected footpads of P2X7-deficient mice. Analysis of the cytokine profile in footpad homogenates showed increased levels of IFN-γ and decreased TGF-β production in P2X7-deficient mice, suggesting an exaggerated pro-inflammatory response. In addition, we observed that CD4+ and CD8+ T cells from infected P2X7-deficient mice exhibit a higher proliferative capacity than infected WT mice. These data suggest that P2X7 receptor plays a key role in parasite control by regulating T effector cells and inflammation during L. amazonensis infection.

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Abbreviations

KO:

Knockout

DPI:

Days postinfection

ROS:

Reactive oxygen species

NO:

Nitric oxide

LTB4:

Leukotriene B4

FBS:

Heat-inactivated foetal bovine serum

CEUA:

Commission for Ethical Use of Research Animals

TCA:

Trichloroacetic acid

GFI-1:

Growth factor-independent 1 transcription repressor

M199:

199 medium

DMEM:

Dulbecco’s modified Eagle’s medium

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Acknowledgements

This work was supported by funds from the Conselho Nacional de Desenvolvimento Cientifico e Tecnológico do Brasil (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), the Programa de Núcleos de Excelência (PRONEX), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), the Instituto Nacional de Ciência e Tecnologia para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica (INPeTAm/UFRJ), and the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).

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Authors and Affiliations

  1. Institute of Biophysics Carlos Chagas Filho, IBCCF/Federal University of Rio de Janeiro – UFRJ, Rio de Janeiro, RJ, 21941-902, Brazil

    Vanessa Ribeiro Figliuolo, Suzana Passos Chaves, Luiz Eduardo Baggio Savio, Maria Luiza Prates Thorstenberg, Christina Maeda Takiya, Herbert Leonel de Matos Guedes, Bartira Rossi-Bergmann & Robson Coutinho-Silva

  2. National Institute of Science and Technology for Translational Research in Health and Environment in the Amazon Region (INPeTAm), Rio de Janeiro, Brazil

    Vanessa Ribeiro Figliuolo, Suzana Passos Chaves, Luiz Eduardo Baggio Savio, Bartira Rossi-Bergmann & Robson Coutinho-Silva

  3. Immunology Department, University of São Paulo – USP, São Paul, Brazil

    Érika Machado Salles & Maria Regina D’Império-Lima

  4. Instituto de Biofísica Carlos Chagas Filho – UFRJ, Edifício do Centro de Ciências da Saúde, Bloco G. Av. Carlos Chagas Filho, 373. Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil

    Robson Coutinho-Silva

Authors
  1. Vanessa Ribeiro Figliuolo
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  2. Suzana Passos Chaves
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  3. Luiz Eduardo Baggio Savio
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  9. Bartira Rossi-Bergmann
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  10. Robson Coutinho-Silva
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Corresponding author

Correspondence to Robson Coutinho-Silva.

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Conflict of interest

Vanessa Ribeiro Figliuolo declares that she has no conflict of interest.

Suzana Passos Chaves declares that she has no conflict of interest.

Luiz Eduardo Baggio Savio declares that he has no conflict of interest.

Maria Luiza Prates Thorstenberg declares that she has no conflict of interest.

Érika Machado Salles declares that she has no conflict of interest.

Christina Maeda Takiya declares that she has no conflict of interest.

Maria Regina D’Império-Lima declares that she has no conflict of interest.

Herbert Leonel de Matos Guedes declares that he has no conflict of interest.

Bartira Rossi-Bergmann declares that she has no conflict of interest.

Robson Coutinho-Silva declares that he has no conflict of interest.

Ethical approval

All animals received care according to institutional guidelines, and all procedures were according to EU guidelines (2010/63) after approval by the Animal Care Committee of the Federal University of Rio de Janeiro.

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Vanessa Ribeiro Figliuolo and Suzana Passos Chaves contributed equally

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Figliuolo, V.R., Chaves, S.P., Savio, L.E.B. et al. The role of the P2X7 receptor in murine cutaneous leishmaniasis: aspects of inflammation and parasite control. Purinergic Signalling 13, 143–152 (2017). https://doi.org/10.1007/s11302-016-9544-1

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