Ecto-nucleotidase activities of promastigotes from leishmania (viannia) braziliensis relates to parasite infectivity and disease clinical outcome
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2012-10
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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 Findings: Our 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/Significance: Our 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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LEITE, Pauline M.; GOMES, RODRIGO S.; FIGUEIREDO, Amanda B.; SERAFIM, Tiago D.; TAFURI, Wagner L.; SOUZA, Carolina C. de; MOURA, Sandra A. L. ; FIETTO, Juliana L. R.; MELO, Maria N.; RIBEIRO-DIAS, Fátima; OLIVEIRA, Milton A. P.; RABELLO, Ana; AFONSO, Luís C. C. Ecto-nucleotidase activities of promastigotes from leishmania (viannia) braziliensis relates to parasite infectivity and disease clinical outcome. PLoS Neglected Tropical Diseases, San Francisco, v. 6, n. 10, e1850, Oct. 2012.