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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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.
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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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DOI: https://doi.org/10.1007/s11302-016-9544-1