E-NTPDase (ecto-nucleoside triphosphate diphosphohydrolase) of Leishmania amazonensis inhibits macrophage activation

Gomes, Rodrigo Saar; Carvalho, Luana Cristina Faria; Vasconcellos, Raphael de Souza; Fietto, Juliana Lopes Rangel; Afonso, Luís Carlos Crocco

doi:10.1016/j.micinf.2014.12.009

Cited by 25 publications

(36 citation statements)

References 48 publications

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“…This is confirmed by the observation of increased Ado levels in serum from visceral leishmaniasis patients [103, 104]. This can cause the prevention of the activation of macrophages and leads to the increase of infection by Leishmania species [105–109]. Moreover, the virulence of L. amazonensis promastigotes could be due to its high ecto-nucleotidase activity [110] (Fig.…”

Section: Reviewmentioning

confidence: 76%

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Crosstalk between purinergic receptors and lipid mediators in leishmaniasis

2016

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Leishmaniasis is a neglected tropical disease affecting millions of people around the world caused by organisms of the genus Leishmania. Parasite escape mechanisms of the immune system confer the possibility of resistance and dissemination of the disease. A group of molecules that has become a target for Leishmania survival strategies are lipid mediators. Among them, leukotriene B4 (LTB4) has been described as a pro-inflammatory molecule capable of activating cells of the immune system to combat Leishmania. In an opposite way, prostaglandin E2 (PGE2) is a lipid mediator described as a deactivator of macrophages and neutrophils. The balance of these two molecules can be generated by extracellular nucleotides, such as adenosine 5'-triphosphate (ATP) and adenosine (Ado), which activate the purinergic receptors system. Herein, we discuss the role of extracellular nucleotides and the resulting balance of LTB4 and PGE2 in Leishmania fate, survival or death.

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Section: Reviewmentioning

confidence: 76%

“…Furthermore, it has been observed that L. amazonensis infection increases ecto-nucleotidases expression in DC [111]. Thus, the blocking of the A 2B receptors is found to increase production of NO and decrease parasite survival, suggesting participation of Ado in this process [109]. …”

Section: Reviewmentioning

confidence: 99%

Crosstalk between purinergic receptors and lipid mediators in leishmaniasis

2016

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“…Recently, Gomes et al demonstrated the role of ENTPDase2 from L. amazonensis in macrophage infection. This paper shows that in Leishmania amazonensis, the pathogenic agent of diffuse Leishmaniasis, the high activity of E-NTPDase-2 at the surface of the parasites, increased the survival rate in LPS/IFN--activated cells [47] . On the other hand, the inhibition of surface E-NTPDase2 led to a lower survival rate and higher macrophage activation.…”

Section: Biochemical and Biological Roles Of Ecto-nucleotidases And Tmentioning

confidence: 79%

“…The GP63, a zinc-metalloprotease named glycoprotein 63 (GP63), is another critical virulence factor that has been fully explored [34][35][36][37][38] . However, the E-NTPDases (ecto-nucleoside triphosphate diphosphohydrolases), while less-extensively studied, have been demonstrated and believed to be important infectivity and virulence factors [39][40][41][42][43][44][45][46][47][48] .…”

Section: Leishmania Braziliensis Is Responsible For Most Cases Of MLmentioning

confidence: 99%

“…The authors also demonstrated that the ecto-nucleotidase activity in L. amazonensis is also related to the inhibition of the inflammatory profile of macrophages. Therefore, the expression of E-NTPDase at the parasite surface plays an important role in the modulation and infection of macrophages [47] .…”

Section: Biochemical and Biological Roles Of Ecto-nucleotidases And Tmentioning

confidence: 99%

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

et al. 2016

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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.

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NTPDase activities: possible roles on Leishmania spp infectivity and virulence

Paes-Vieira

Gomes-Vieira

Meyer‐Fernandes

2018

Cell Biology International

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Nucleoside triphosphate diphosphohydrolases (NTPDases) are enzymes that belong to the GDA1/CD39 protein superfamily. These enzymes catalyze the hydrolysis of ATP and ADP to the monophosphate form (AMP). Biochemical characterization of the nucleotidases/NTPDases from various types of cells, including those from plants, animals, and pathogenic organisms, has revealed the existence of several isoforms with different specificities with respect to divalent cations (magnesium, calcium, manganese, and zinc) and substrates. In mammals, the NTPDases play important roles in the regulation of thrombosis and inflammation. In parasites of the genus Leishmania, the causative agents of leishmaniasis, two NTPDase isoforms, termed NTPDase-1 and NTPDase-2 have been described. Independently of their cellular localization, whether cell-surface localized, secreted or targeted to other organelles, in some Leishmania species these NTPDases could be involved in parasite growth, infectivity, and virulence. Experimental evidence has suggested that the hydrolysis of ATP and ADP by parasite ecto-nucleotidases can down-modulate the host immune response. In this context, the present work provides an overview of recent works that show strong evidence not only of the involvement of the nucleotidases/NTPDases in Leishmania spp infectivity and virulence but also of the molecular mechanisms that lead to the success of the parasitic infection.

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E-NTPDase (ecto-nucleoside triphosphate diphosphohydrolase) of Leishmania amazonensis inhibits macrophage activation

Cited by 25 publications

References 48 publications

Crosstalk between purinergic receptors and lipid mediators in leishmaniasis

Crosstalk between purinergic receptors and lipid mediators in leishmaniasis

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

NTPDase activities: possible roles on Leishmania spp infectivity and virulence

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