Insulin-like growth factor-I induced and constitutive arginase activity differs among isolates of Leishmania derived from patients with diverse clinical forms of Leishmania braziliensis infection

Vendrame, Célia Maria Vieira; Souza, Luana Dias de; Carvalho, Matheus Furtado de; Salgado, Katia; Carvalho, Edgar M.; Goto, Hiro

doi:10.1016/j.trstmh.2010.03.007

Cited by 14 publications

(14 citation statements)

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“…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]. In addition, isolates obtained from patients with mucosal leishmaniasis are more resistant to NO when compared to isolates obtained from patients with cutaneous leishmaniasis [13].…”

Section: Resultsmentioning

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: Resultsmentioning

confidence: 99%

“…Although the involvement of host immune response [4], [5], [9]–[12], and, a limited number of parasite factors also have lately been recognized as important [13], [14].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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“…This latter regulatory mechanism has since been challenged (Muleme et al, 2009). Indeed, metastatic L. braziliensis species were reported to induce higher levels of insulin-like growth factor (IGF), a substance known to up-regulate arginase activity (Vendrame et al, 2010). None of these reports, however, have addressed the possible influence of LRV infection on oxidative resistance.…”

Section: Immune Response In MCL Patientsmentioning

confidence: 99%

Leishmania RNA virus: when the host pays the toll

Hartley

Ronet

Zangger

et al. 2012

Front. Cell. Inf. Microbio.

126

143

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The presence of an RNA virus in a South American subgenus of the Leishmania parasite, L. (Viannia), was detected several decades ago but its role in leishmanial virulence and metastasis was only recently described. In Leishmania guyanensis, the nucleic acid of Leishmania RNA virus (LRV1) acts as a potent innate immunogen, eliciting a hyper-inflammatory immune response through toll-like receptor 3 (TLR3). The resultant inflammatory cascade has been shown to increase disease severity, parasite persistence, and perhaps even resistance to anti-leishmanial drugs. Curiously, LRVs were found mostly in clinical isolates prone to infectious metastasis in both their human source and experimental animal model, suggesting an association between the viral hyperpathogen and metastatic complications such as mucocutaneous leishmaniasis (MCL). MCL presents as chronic secondary lesions in the mucosa of the mouth and nose, debilitatingly inflamed and notoriously refractory to treatment. Immunologically, this outcome has many of the same hallmarks associated with the reaction to LRV: production of type 1 interferons, bias toward a chronic Th1 inflammatory state and an impaired ability of host cells to eliminate parasites through oxidative stress. More intriguing, is that the risk of developing MCL is found almost exclusively in infections of the L. (Viannia) subtype, further indication that leishmanial metastasis is caused, at least in part, by a parasitic component. LRV present in this subgenus may contribute to the destructive inflammation of metastatic disease either by acting in concert with other intrinsic “metastatic factors” or by independently preying on host TLR3 hypersensitivity. Because LRV amplifies parasite virulence, its presence may provide a unique target for diagnostic and clinical intervention of metastatic leishmaniasis. Taking examples from other members of the Totiviridae virus family, this paper reviews the benefits and costs of endosymbiosis, specifically for the maintenance of LRV infection in Leishmania parasites, which is often at the expense of its human host.

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“…The dsRNA virus seems to interfere with NO production for another via: metastatic L. braziliensis species induce higher levels of insulin-like growth factor (IGF) which is able to promote upregulation on the arginase activity [ 116 ]. However, this kind of report does not have to investigate the possible influence of LRV infection on oxidative resistance [ 115 ].…”

Section: Immune Response Against Leishmania Andmentioning

confidence: 99%

The Dialogue of the Host-Parasite Relationship:Leishmaniaspp. andTrypanosoma cruziInfection

Morais

Lima

Terra

et al. 2015

BioMed Research International

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The intracellular protozoa Leishmania spp. and Trypanosoma cruzi and the causative agents of Leishmaniasis and Chagas disease, respectively, belong to the Trypanosomatidae family. Together, these two neglected tropical diseases affect approximately 25 million people worldwide. Whether the host can control the infection or develops disease depends on the complex interaction between parasite and host. Parasite surface and secreted molecules are involved in triggering specific signaling pathways essential for parasite entry and intracellular survival. The recognition of the parasite antigens by host immune cells generates a specific immune response. Leishmania spp. and T. cruzi have a multifaceted repertoire of strategies to evade or subvert the immune system by interfering with a range of signal transduction pathways in host cells, which causes the inhibition of the protective response and contributes to their persistence in the host. The current therapeutic strategies in leishmaniasis and trypanosomiasis are very limited. Efficacy is variable, toxicity is high, and the emergence of resistance is increasingly common. In this review, we discuss the molecular basis of the host-parasite interaction of Leishmania and Trypanosoma cruzi infection and their mechanisms of subverting the immune response and how this knowledge can be used as a tool for the development of new drugs.

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Insulin-like growth factor-I induced and constitutive arginase activity differs among isolates of Leishmania derived from patients with diverse clinical forms of Leishmania braziliensis infection

Cited by 14 publications

References 6 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

Leishmania RNA virus: when the host pays the toll

The Dialogue of the Host-Parasite Relationship:Leishmaniaspp. andTrypanosoma cruziInfection

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