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

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.

The P2X7 Receptor in Inflammatory Diseases: Angel or Demon?

“…In a mouse model where subcutaneous L. amazonensis infection is induced by subcutaneous injection of the parasite in the footpad, genetic deletion of P2X7 receptor resulted in increased cell infiltration, higher IFN-γ levels, and low concentrations of IL-17 and TGF-β in the footpad, suggesting an excessive pro-inflammatory response. In addition to that, CD4 + and CD8 + T cells from infected P2X7 KO mice exhibited higher proliferative capacity than cells from infected WT mice (Figliuolo et al, 2017a ). P2X7 KO mice were more susceptible to L. amazonensis infection showing increased lesion size and parasitic load (Figliuolo et al, 2017a ).…”

“…In addition to that, CD4 + and CD8 + T cells from infected P2X7 KO mice exhibited higher proliferative capacity than cells from infected WT mice (Figliuolo et al, 2017a ). P2X7 KO mice were more susceptible to L. amazonensis infection showing increased lesion size and parasitic load (Figliuolo et al, 2017a ). Increased susceptibility of P2X7 KO mice to L. amazonensis might be related to the role of P2X7 receptor in controlling T cell proliferation by inducing apoptosis.…”

“…Increased susceptibility of P2X7 KO mice to L. amazonensis might be related to the role of P2X7 receptor in controlling T cell proliferation by inducing apoptosis. P2X7 KO mice showed an excessive CD4 + T cell proliferation which has a pathogenic role in leishmaniasis (Figliuolo et al, 2017a ). Thus, P2X7 receptor is crucial for the immune response during leishmaniasis by regulating both innate and adaptive immunity.…”

Purinergic Signalling: Therapeutic Developments

“…The dysfunction of P1, P2Y and P2X7R and NTPDases are likely to contribute to morbidity due to human schistosomiasis ( Silva, 2016 ). P2X7R are important in parasite control as they regulate T effector cells and inflammation during L. amazonensis infection ( Figliuolo et al, 2017a ). A commentary about ATP as an initiator of immunity to parasitic infections has been published ( Nelson et al, 2017 ).…”

Spergulin-A strives intra-macrophage leishmanicidal activity by regulating the host P2X7R-P38MAPK axis

“…P2X 7 R receptor activation was found to be helpful in reducing L. amazonensis parasitic load in macrophages via leukotriene B4 (LTB4) production(Chaves et al, 2009). Interestingly enough, P2X 7 knock out mice were observed to possess increased lesion size and the parasitic load of L. amazonensis with an unwarranted CD4 + T cell proliferation(Figliuolo et al, 2017). P2X 7 R activation with extracellular stimuli like ATP can initiate opening of cationspecific ion channel and result in the influx of Ca ++ and the efflux of K + and with extended exposure able to create pores in the plasma membrane resulted in the passage of larger molecules(Miller et al, 2011).…”