Document Detail

Ecto-nucleotidase activities of promastigotes from Leishmania (Viannia) braziliensis relates to parasite infectivity and disease clinical outcome.
MedLine Citation:
PMID:  23071853     Owner:  NLM     Status:  MEDLINE    
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.
Pauline M Leite; Rodrigo S Gomes; Amanda B Figueiredo; Tiago D Serafim; Wagner L Tafuri; Carolina C de Souza; Sandra A L Moura; Juliana L R Fietto; Maria N Melo; Fátima Ribeiro-Dias; Milton A P Oliveira; Ana Rabello; Luís C C Afonso
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-11
Journal Detail:
Title:  PLoS neglected tropical diseases     Volume:  6     ISSN:  1935-2735     ISO Abbreviation:  PLoS Negl Trop Dis     Publication Date:  2012  
Date Detail:
Created Date:  2012-10-16     Completed Date:  2013-03-01     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101291488     Medline TA:  PLoS Negl Trop Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1850     Citation Subset:  IM    
Laboratório de Imunoparasitologia, DECBI/NUPEB, Universidade Federal de Ouro Preto, Minas Gerais, Brazil.
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MeSH Terms
Adenine Nucleotides / metabolism
Adenosine Triphosphatases / biosynthesis*
Cell Line
Disease Models, Animal
Immune Evasion*
Leishmania braziliensis / enzymology*,  pathogenicity*
Leishmaniasis, Mucocutaneous / parasitology*,  pathology*
Macrophages / immunology,  parasitology
Mice, Inbred C57BL
Nitric Oxide / metabolism
Virulence Factors / biosynthesis*
Reg. No./Substance:
0/Adenine Nucleotides; 0/Virulence Factors; 10102-43-9/Nitric Oxide; EC 3.6.1.-/Adenosine Triphosphatases; EC 3.6.1.-/ectoATPase

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