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Lutzomyia longipalpis saliva drives apoptosis and enhances parasite burden in neutrophils.
- Source :
-
Journal of leukocyte biology [J Leukoc Biol] 2011 Sep; Vol. 90 (3), pp. 575-82. Date of Electronic Publication: 2011 Jun 17. - Publication Year :
- 2011
-
Abstract
- Neutrophils are considered the host's first line of defense against infections and have been implicated in the immunopathogenesis of Leishmaniasis. Leishmania parasites are inoculated alongside vectors' saliva, which is a rich source of pharmacologically active substances that interfere with host immune response. In the present study, we tested the hypothesis that salivary components from Lutzomyia longipalpis, an important vector of visceral Leishmaniasis, enhance neutrophil apoptosis. Murine inflammatory peritoneal neutrophils cultured in the presence of SGS presented increased surface expression of FasL and underwent caspase-dependent and FasL-mediated apoptosis. This proapoptosis effect of SGS on neutrophils was abrogated by pretreatment with protease as well as preincubation with antisaliva antibodies. Furthermore, in the presence of Leishmania chagasi, SGS also increased apoptosis on neutrophils and increased PGE(2) release and decreased ROS production by neutrophils, while enhancing parasite viability inside these cells. The increased parasite burden was abrogated by treatment with z-VAD, a pan caspase inhibitor, and NS-398, a COX-2 inhibitor. In the presence of SGS, Leishmania-infected neutrophils produced higher levels of MCP-1 and attracted a high number of macrophages by chemotaxis in vitro assays. Both of these events were abrogated by pretreatment of neutrophils with bindarit, an inhibitor of CCL2/MCP-1 expression. Taken together, our data support the hypothesis that vector salivary proteins trigger caspase-dependent and FasL-mediated apoptosis, thereby favoring Leishmania survival inside neutrophils, which may represent an important mechanism for the establishment of Leishmania infection.
- Subjects :
- Animals
Caspases metabolism
Chemokine CCL2 metabolism
Chemotaxis
Fas Ligand Protein metabolism
Female
Host-Parasite Interactions
Immunoblotting
Leishmania
Leishmaniasis parasitology
Macrophages immunology
Male
Mice
Mice, Inbred C57BL
Neutrophils immunology
Psychodidae parasitology
Reactive Oxygen Species metabolism
Saliva chemistry
Saliva parasitology
Salivary Glands cytology
Salivary Glands immunology
Salivary Glands parasitology
Apoptosis
Leishmaniasis immunology
Neutrophils parasitology
Neutrophils pathology
Psychodidae immunology
Saliva immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1938-3673
- Volume :
- 90
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of leukocyte biology
- Publication Type :
- Academic Journal
- Accession number :
- 21685247
- Full Text :
- https://doi.org/10.1189/jlb.0211105