The Leishmania-Macrophage Interactions: Role of E-NTPDases and Purinergic Signaling

Abstract

Leishmaniasis comprises a group of diseases caused by protozoan parasites of the genus Leishmania. The transmission occurs by the bite of phlebotomine female sand flies of the genera Phlebotomus and Lutzomyia. In the mammalian host, these parasites infect and proliferate mainly into the macrophages, avoiding the harmful effects of the innate inflammatory response. It has been reported in several works that purinergic signaling, including purine receptors P1 and P2, are dynamically modulated during both the development and activation of cells from the immune system to achieve homeostasis or combat infections as well as harmful damage. Many pathogens are able to subvert the host immune response in order to promote the success or maintenance of infection. This subversion can be related to the influence of pathogens on purinergic signaling leading to decreased levels of the pro-inflammatory molecule ATP and increased levels of the immunosuppressive molecule adenosine. This scenario can be produced as the final product of the joint activity of E-NTPDases and 5'-ectonucleotidases. Thus, this review will discuss the cellular and molecular events occurring during the interaction of Leishmania and macrophages focusing on the purinergic signaling pathways and their relationships with ENTPDases from pathogenic species of Leishmania.

E-NTPDases: Possible Roles on Host-Parasite Interactions and Therapeutic Opportunities

“…Since E-NTPDases have been implicated in different processes of parasite physiology, such as differentiation, nutrition, invasion, survival in the host cell, and modulation of the host immune response to establish infection, these enzymes have been seen as promising targets for drug development ( Paes-Vieira et al., 2018 ). In this sense, many works have shown the effects of several compounds on parasite E-NTPDases ( Knowles, 2011 ; Pimentel et al., 2016 ; de Carvalho et al., 2019 ; da Silva et al., 2021 ).…”

“…, Trichomonas vaginalis, Tritrichomonas foetus, Toxoplasma gondii, and Schistosoma spp. ( Berrêdo-Pinho et al., 2001 ; Meyer-Fernandes, 2002 ; Sansom, 2012 ; Pimentel et al., 2016 ; Paes-Vieira et al., 2018 ).…”