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- Title
Infection with Leishmania amazonensis upregulates purinergic receptor expression and induces host-cell susceptibility to UTP-mediated apoptosis.
- Authors
Marques-da-Silva, Camila; Chaves, Mariana M.; Chaves, Suzana Passos; Figliuolo, Vanessa Ribeiro; Meyer-Fernandes, José Roberto; Corte-Real, Suzana; Lameu, Claudiana; Ulrich, Henning; Ojcius, David M.; Rossi-Bergmann, Bartira; Coutinho-Silva, Robson
- Abstract
Summary 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 Ca2+ changes. Infection of macrophages with Leishmania upregulated the expression of P2Y2 and P2Y4 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.
- Subjects
LEISHMANIASIS; PURINERGIC receptors; APOPTOSIS; INTRACELLULAR calcium; HOST-parasite relationships; MACROPHAGES; MESSENGER RNA
- Publication
Cellular Microbiology, 2011, Vol 13, Issue 9, p1410
- ISSN
1462-5814
- Publication type
Article
- DOI
10.1111/j.1462-5822.2011.01630.x