Immune and inflammatory responses to Leishmania amazonensis isolated from different clinical forms of human leishmaniasis in CBA mice

Souza, Valderes Lemos de; Veras, Patrícia Sampaio Tavares; Welby-Borges, Marcus; Silva, Tânia M C; Leite, Bruna R; Ferraro, Rodrigo B.; Meyer‐Fernandes, José Roberto; Barral, Aldina; Costa, Jackson Maurício Lopes; Freitas, Luiz Antônio Rodrigues de

doi:10.1590/s0074-02762011000100004

Cited by 23 publications

(25 citation statements)

References 25 publications

(33 reference statements)

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“…The delay in lesion development as a result of the increased ecto-ATPase activity of the parasite was recently demonstrated in a study using L. (L.) amazonensis isolates obtained from patients with different clinical forms [21]. Our results expand on this observation indicating that not only the reduction of extracellular ATP, but also, the increase in extracellular Ado may play an important role in stalling the immune response.…”

Section: Resultssupporting

confidence: 81%

“…The fact that different strains of the same parasite species are able to cause distinct outcomes in isogenic mice (this study and [21], [74]) indicates that parasite specific factors may also contribute to the result of the infection. According to Vendrame et al (2010), the high arginase activity of isolates from mucosal cases suggests that this characteristic favored the development of mucosal lesions and contributed to the survival and proliferation of Leishmania in a hostile environment [14].…”

Section: Resultsmentioning

confidence: 69%

“…These factors are involved in the establishment of intracellular parasitism as well as in the inhibition of host immune response [15], [16]. Components of extracellular ATP metabolism pathway are emerging candidates to determine the virulence of these parasites, since ATP and adenosine (Ado), a product of AMP hydrolysis, are able to influence the immunological response of the host and, in consequence, the parasite establishment [17]–[21].…”

Section: Introductionmentioning

confidence: 99%

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Ecto-Nucleotidase Activities of Promastigotes from Leishmania (Viannia) braziliensis Relates to Parasite Infectivity and Disease Clinical Outcome

et al. 2012

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Background Leishmania (Viannia) braziliensis has been associated with a broad range of clinical manifestations ranging from a simple cutaneous ulcer to destructive mucosal lesions. Factors leading to this diversity of clinical presentations are not clear, but parasite factors have lately been recognized as important in determining disease progression. Given the fact that the activity of ecto-nucleotidases correlates with parasitism and the development of infection, we evaluated the activity of these enzymes in promastigotes from 23 L. braziliensis isolates as a possible parasite-related factor that could influence the clinical outcome of the disease.Methodology/Principal FindingsOur results show that the isolates differ in their ability to hydrolyze adenine nucleotides. Furthermore, we observed a positive correlation between the time for peak of lesion development in C57BL/6J mice and enzymatic activity and clinical manifestation of the isolate. In addition, we found that L. (V.) braziliensis isolates obtained from mucosal lesions hydrolyze higher amounts of adenine nucleotides than isolates obtained from skin lesions. One isolate with high (PPS6m) and another with low (SSF) ecto-nucleotidase activity were chosen for further studies. Mice inoculated with PPS6m show delayed lesion development and present larger parasite loads than animals inoculated with the SSF isolate. In addition, PPS6m modulates the host immune response by inhibiting dendritic cell activation and NO production by activated J774 macrophages. Finally, we observed that the amastigote forms from PPS6m and SSF isolates present low enzymatic activity that does not interfere with NO production and parasite survival in macrophages.Conclusions/SignificanceOur data suggest that ecto-nucleotidases present on the promastigote forms of the parasite may interfere with the establishment of the immune response with consequent impaired ability to control parasite dissemination and this may be an important factor in determining the clinical outcome of leishmaniasis.

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Section: Resultssupporting

confidence: 81%

Section: Resultsmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

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Ecto-Nucleotidase Activities of Promastigotes from Leishmania (Viannia) braziliensis Relates to Parasite Infectivity and Disease Clinical Outcome

et al. 2012

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“…Consistent with this, inhibition of adenosine receptor A 2B led to decreased lesion size and lower parasite burden [43]. In clinical practice, results that are consistent with the idea that ecto-ATPase activity is involved in virulence were also observed, whereby L. amazonensis strain isolated from a human case of VL possess higher ecto-ATPase activity than strains isolated from CL cases [44]. …”

Section: Adenosine and The Establishment Of Leishmania Infection: mentioning

confidence: 56%

Adenosine and Immune Imbalance in Visceral Leishmaniasis: The Possible Role of Ectonucleotidases

Paletta-Silva

Meyer‐Fernandes

2012

Journal of Tropical Medicine

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Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is responsible for most Leishmania-associated deaths. VL represents a serious public health problem that affects many countries. The immune response in leishmaniasis is very complex and is poorly understood. The Th1 versus Th2 paradigm does not appear to be so clear in visceral leishmaniasis, suggesting that other immunosuppressive or immune-evasion mechanisms contribute to the pathogenesis of VL. It has been demonstrated that generation of adenosine, a potent endogenous immunosuppressant, by extracellular enzymes capable to hydrolyze adenosine tri-nucleotide (ATP) at the site of infection, can lead to immune impairment and contribute to leishmaniasis progression. In this regard, this paper discusses the unique features in VL immunopathogenesis, including a possible role for ectonucleotidases in leishmaniasis.

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“…Similar results were obtained in L. amazonensis : mice inoculated with an isolate that presents higher ecto-ADPase and 5′nucleotidase activities have developed necrotic and ulcerated lesions displaying an infi ltrate rich in parasitized macrophages. On the other hand, the inoculation of an isolate that presents lower activities induced smaller lesions and a mixed infl ammatory infi ltrate, without necrosis or ulceration (Souza et al 2011 ).…”

Section: Possible Roles Of Ecto-nucleotidases In Virulencementioning

confidence: 99%

Ecto-nucleotidases and Ecto-phosphatases from Leishmania and Trypanosoma Parasites

Freitas-Mesquita

Meyer‐Fernandes

2013

Subcellular Biochemistry

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Ecto-enzymes can be defined as membrane-bound proteins that have their active site facing the extracellular millieu. In trypanosomatids, the physiological roles of these enzymes remain to be completed elucidated; however, many important events have already been related to them, such as the survival of parasites during their complex life cycle and the successful establishment of host infection. This chapter focuses on two remarkable classes of ecto-enzymes: ecto-nucleotidases and ecto-phosphatases, summarizing their occurrence and possible physiological roles in Leishmania and Trypanosoma genera. Ecto-nucleotidases are characterized by their ability to hydrolyze extracellular nucleotides, playing an important role in purinergic signaling. By the action of these ecto-enzymes, parasites are capable of modulating the host immune system, which leads to a successful parasite infection. Furthermore, ecto-nucleotidases are also involved in the purine salvage pathway, acting in the generation of nucleosides that are able to cross plasma membrane via specialized transporters. Another important ecto-enzyme present in a vast number of pathogenic organisms is the ecto-phosphatase. These enzymes are able to hydrolyze extracellular phosphorylated substrates, releasing free inorganic phosphate that can be internalized by the cell, crossing the plasma membrane through a Pi-transporter. Ecto-phosphatases are also involved in the invasion and survival of parasite in the host cells. Several alternative functions have been suggested for these enzymes in parasites, such as participation in their proliferation, differentiation, nutrition and protection. In this context, the present chapter provides an overview of recent discoveries related to the occurrence of ecto-nucleotidase and ecto-phosphatase activities in Leishmania and Trypanosoma parasites.

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Immune and inflammatory responses to Leishmania amazonensis isolated from different clinical forms of human leishmaniasis in CBA mice

Cited by 23 publications

References 25 publications

Ecto-Nucleotidase Activities of Promastigotes from Leishmania (Viannia) braziliensis Relates to Parasite Infectivity and Disease Clinical Outcome

Ecto-Nucleotidase Activities of Promastigotes from Leishmania (Viannia) braziliensis Relates to Parasite Infectivity and Disease Clinical Outcome

Adenosine and Immune Imbalance in Visceral Leishmaniasis: The Possible Role of Ectonucleotidases

Ecto-nucleotidases and Ecto-phosphatases from Leishmania and Trypanosoma Parasites

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