Adenosine and immune imbalance in visceral leishmaniasis: the possible role of ectonucleotidases

Abstract

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.

Figure 1

Partial reactions catalyzed by ecto-nucleoidases: (1) ecto-ATPase, ectonucleoside triphosphate diphosphohydrolase; (2) ecto-5′-nucleotidase; (3) ecto-3′-nucleotidase. The sequential hydrolysis of extracellular ATP by Leishmania ectonucleotidases triggers the host inflammatory and immune response following P2 receptor activation by extracellular ATP (blue square) and P1 (A₂) receptors activation by extracellular adenosine nucleoside (yellow square). ADO: Adenosine.