Lutzomyia longipalpis saliva drives apoptosis and enhances parasite burden in neutrophils

Salivary proteins from Lutzomyia longipalpis induce host neutrophil caspase‐dependent apoptosis and infection by Leishmania chagasi. Neutrophils are considered the hostˈs first line of defense against infections and have been implicated in the immunopathogenesis of Leishmaniasis. Leishmania parasite...

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Published in:Journal of leukocyte biology 2011-09, Vol.90 (3), p.575-582
Main Authors: Prates, Deboraci Brito, Araújo‐Santos, Théo, Luz, Nívea Farias, Andrade, Bruno B., França‐Costa, Jaqueline, Afonso, Lilian, Clarêncio, Jorge, Miranda, José Carlos, Bozza, Patrícia T., DosReis, George A., Brodskyn, Cláudia, Barral‐Netto, Manoel, Borges, Valéria Matos, Barral, Aldina
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Caspases - metabolism
cell death
Chemokine CCL2 - metabolism
Chemotaxis
Fas Ligand Protein - metabolism
FasL
Female
Host-Parasite Interactions
Immunoblotting
Leishmania
Leishmania chagasi
Leishmaniasis - immunology
Leishmaniasis - parasitology
Lutzomyia longipalpis
Macrophages - immunology
Male
Mice
Mice, Inbred C57BL
Neutrophils - immunology
Neutrophils - parasitology
Neutrophils - pathology
Psychodidae - immunology
Psychodidae - parasitology
Reactive Oxygen Species - metabolism
Saliva - chemistry
Saliva - immunology
Saliva - parasitology
Salivary Glands - cytology
Salivary Glands - immunology
Salivary Glands - parasitology
sand fly
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Summary:Salivary proteins from Lutzomyia longipalpis induce host neutrophil caspase‐dependent apoptosis and infection by Leishmania chagasi. Neutrophils are considered the hostˈs first line of defense against infections and have been implicated in the immunopathogenesis of Leishmaniasis. Leishmania parasites are inoculated alongside vectorsˈ 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 PGE2 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.
ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.0211105