Infection with Leishmania amazonensis upregulates purinergic receptor expression and induces host-cell susceptibility to UTP-mediated apoptosis.

Abstract

Nucleotides are released into the extracellular milieu from infected cells and cells at inflammatory sites. The extracellular nucleotides bind to specific purinergic (P2) receptors and thereby induce a variety of cellular responses including anti-parasitic effects. Here we investigated whether extracellular nucleotides affect leishmanial infection in macrophages, and found that UTP reduces strongly the parasite load in peritoneal macrophages. Ultrastructural analysis of infected cells revealed that UTP induced morphological damage in the intracellular parasites. Uridine nucleotides also induced dose-dependent apoptosis of macrophages and production of ROI and RNI only in infected macrophages. The intracellular calcium measurements of infected cells showed that the response to UTP, but not UDP, increased the sensitivity and amplitude of cytosolic Ca(2+) changes. Infection of macrophages with Leishmania upregulated the expression of P2Y(2) and P2Y(4) receptor mRNA. The data suggest indirectly that Leishmania amazonensis infection induces modulation and heteromerization of P2Y receptors on macrophages. Thus UTP modulates the host response against L. amazonensis infection. UTP and UTP homologues should therefore be considered as novel components of therapeutic strategies against cutaneous leishmaniasis.

• Authors: Camila Marques-da-Silva, Mariana M Chaves, Suzana Passos Chaves, Vanessa Ribeiro Figliuolo, José Roberto Meyer-Fernandes, Suzana Corte-Real, Claudiana Lameu, Henning Ulrich, David M Ojcius, Bartira Rossi-Bergmann, Robson Coutinho-Silva
• Journal: Cellular microbiology (Cell Microbiol) Vol. 13 Issue 9 Pg. 1410-28 (Sep 2011) ISSN: 1462-5822 [Electronic] India
• PMID: 21740498 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Blackwell Publishing Ltd.

Chemical References

• Reactive Oxygen Species
• Receptors, Purinergic
• Receptors, Purinergic P2
• Superoxides
• L-Lactate Dehydrogenase
• Uridine Triphosphate

Topics

• Animals
• Apoptosis (genetics, physiology)
• Blotting, Western
• Cells, Cultured
• In Situ Nick-End Labeling
• L-Lactate Dehydrogenase
• Leishmania (pathogenicity, physiology)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Microscopy, Electron
• Polymerase Chain Reaction
• Reactive Oxygen Species (metabolism)
• Receptors, Purinergic (genetics, metabolism)
• Receptors, Purinergic P2 (genetics, metabolism)
• Superoxides (metabolism)
• Uridine Triphosphate (metabolism)