The influence of ecto-nucleotidases on Leishmania amazonensis infection and immune response in C57B/6 mice

• Published in: Acta tropica 2010-09, Vol.115 (3), p.262-269
• Main Authors: de Souza, Miriam Conceição, de Assis, Elisângela Aparecida, Gomes, Rodrigo Saar, Marques da Silva, Eduardo de Almeida, Melo, Maria Norma, Fietto, Juliana Lopes Rangel, Afonso, Luís Carlos Crocco
• Format: Article
• Language: English
• Subjects: Adenosine; Animals; Biological and medical sciences; Chemokine CCL2 - biosynthesis; Chemokine CXCL10 - biosynthesis; Chemokines; e-NTPDase; Female; General aspects; Human protozoal diseases; Infectious diseases; Interferon-gamma - secretion; Leishmania - enzymology; Leishmania - immunology; Leishmania - pathogenicity; Leishmania amazonensis; Leishmaniasis - parasitology; Leishmaniasis - pathology; Leshmaniasis; Macrophage; Macrophages - parasitology; Medical sciences; Mice; Mice, Inbred C57BL; Nucleotidases - biosynthesis; Parasitic diseases; Protozoal diseases; Protozoan Proteins - biosynthesis; Serial Passage; Virulence; Virulence Factors - biosynthesis
• ISSN: 0001-706X; 1873-6254
• DOI: 10.1016/j.actatropica.2010.04.007

Reduced infectivity of Leishmania amazonensis due to prolonged in vitro culture is associated with decreased ecto-nucleotidase activity and altered immune response. Previous results from our laboratory and from the literature have implicated the expression of ecto-nucleotidases in the establishment of Leishmania infection. In the present study we evaluated the correlation between ecto-nucleotidasic activity and the infectivity of L. amazonensis promastigotes that were kept in culture for short or extended numbers of passages, a condition that is known to decrease parasite infectivity. We also analyzed the immune response associated with the infection by these parasites. As expected, we found that long-term cultured parasites induce the development of smaller lesions than the short-term cultured counterparts. Interestingly, long-term cultured parasites presented reduced ecto-nucleotidasic activity. In addition, cells recovered from animals infected with long-term cultured parasites produced higher amounts of IFN-γ and have smaller parasite load, after 8 weeks of infection. Furthermore, after 1 week of infection, there is increased expression of the chemokine CCL2 mRNA in animals infected with short-term cultured parasites. Finally, infection of peritoneal macrophages by these parasites also shows marked differences. Thus, while short-term cultured parasites are able to infect a greater proportion of macrophages, cells infected by long-term cultured parasites express higher amounts of CXCL10 mRNA, which may activate these cells to kill the parasites. We suggest that the enzymes involved in metabolism of extracellular nucleotides may have an important role in infection by L. amazonensis, by acting directly in its adhesion to target cells and by modulating host cell chemokine production.