Lundep, a Sand Fly Salivary Endonuclease Increases Leishmania Parasite Survival in Neutrophils and Inhibits XIIa Contact Activation in Human Plasma

Chagas, Andrezza Campos; Oliveira, Fabiano; Debrabant, Alain; Valenzuela, Jesús G.; Ribeiro, José M. C.; Calvo, Eric

doi:10.1371/journal.ppat.1003923

Cited by 95 publications

(84 citation statements)

References 36 publications

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“…Following this event, there is rapid accumulation of neutrophils [20] and it has been shown that the co-inoculated salivary molecules can modulate neutrophil function [33,34]. Herein, we confirmed neutrophil infiltration to the site of L .…”

Section: Discussionsupporting

confidence: 73%

Exposure to Leishmania braziliensis Triggers Neutrophil Activation and Apoptosis

et al. 2015

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BackgroundNeutrophils are the first line of defense against invading pathogens and are rapidly recruited to the sites of Leishmania inoculation. During Leishmania braziliensis infection, depletion of inflammatory cells significantly increases the parasite load whereas co-inoculation of neutrophils plus L. braziliensis had an opposite effect. Moreover, the co-culture of infected macrophages and neutrophils also induced parasite killing leading us to ask how neutrophils alone respond to an L. braziliensis exposure. Herein we focused on understanding the interaction between neutrophils and L. braziliensis, exploring cell activation and apoptotic fate.Methods and FindingsInoculation of serum-opsonized L. braziliensis promastigotes in mice induced neutrophil accumulation in vivo, peaking at 24 h. In vitro, exposure of thyoglycollate-elicited inflammatory or bone marrow neutrophils to L. braziliensis modulated the expression of surface molecules such as CD18 and CD62L, and induced the oxidative burst. Using mCherry-expressing L. braziliensis, we determined that such effects were mainly observed in infected and not in bystander cells. Neutrophil activation following contact with L. braziliensis was also confirmed by the release of TNF-α and neutrophil elastase. Lastly, neutrophils infected with L. braziliensis but not with L. major displayed markers of early apoptosis.ConclusionsWe show that L. braziliensis induces neutrophil recruitment in vivo and that neutrophils exposed to the parasite in vitro respond through activation and release of inflammatory mediators. This outcome may impact on parasite elimination, particularly at the early stages of infection.

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Section: Discussionsupporting

confidence: 73%

Exposure to Leishmania braziliensis Triggers Neutrophil Activation and Apoptosis

et al. 2015

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“…L. infantum (HYG) was derived from L. infantum (MHOM/ES/92/LLM-320; isoenzyme typed MON-1) (27), provided by Diane MacMahon-Pratt (Yale School of Public Health, New Haven, CT). Wild-type L. infantum promastigotes were transfected with the RFP/Hyg expression cassette and selected on hygromycin B-containing agar plates as described (36). The integration of the expression cassette into the 18S rRNA locus in selected drug-resistant clones was verified by PCR.…”

Section: Methodsmentioning

confidence: 99%

Cross-species genetic exchange between visceral and cutaneous strains of Leishmania in the sand fly vector

Romano

Inbar

Debrabant

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Protozoan parasites of the genus Leishmania are transmitted by sand flies and produce diseases in humans ranging from localized cutaneous lesions to fatal visceral infection. Although these clinical outcomes have clear parasite species associations, the genes controlling these differences are not known. We provide, to our knowledge, the first experimental demonstration of genetic exchange in the sand fly vector between different Leishmania species: a cutaneous strain of Leishmania major and a visceral strain of Leishmania infantum. Eleven full genomic hybrids were generated that displayed differences in their ability to grow in the skin or viscera of mice, indicating that the genes controlling these traits may be polymorphic within the parental species and are potentially amenable to identification by classical linkage analysis.

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“…Polyclonal antibodies against recombinant Aegyptin (7) were raised in rabbits by Spring Valley Laboratories as described in ref. 37.…”

Section: Methodsmentioning

confidence: 99%

Collagen-binding protein, Aegyptin, regulates probing time and blood feeding success in the dengue vector mosquito, Aedes aegypti

Chagas

Ramirez

Jasinskiene

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Mosquito salivary glands have important roles in blood feeding and pathogen transmission. However, the biological relevance of many salivary components has yet to be determined. Aegyptin, a secreted salivary protein from Aedes aegypti, binds collagen and inhibits platelet aggregation and adhesion. We used a transgenic approach to study the relevance of Aegyptin in mosquito blood feeding. Aedes aegypti manipulated genetically to express genespecific inverted-repeat RNA sequences exhibited significant reductions in Aegyptin mRNA accumulation (85-87%) and protein levels (>80-fold) in female mosquito salivary glands. Transgenic mosquitoes had longer probing times (78-300 s, P < 0.0001) when feeding on mice compared with controls (15-56 s), feeding success was reduced, and those feeding took smaller blood meals. However, no differences in feeding success or blood meal size were found in membrane feeding experiments using defibrinated human blood. Salivary gland extracts from transgenic mosquitoes failed to inhibit collagen-induced platelet aggregation in vitro. Reductions of Aegyptin did not affect salivary ADP-induced platelet aggregation inhibition or disturb anticlotting activities. Our results demonstrate the relevance of Aegyptin for A. aegypti blood feeding, providing further support for the hypothesis that platelet aggregation inhibition is a vital salivary function in blood feeding arthropods. It has been suggested that the multiple mosquito salivary components mediating platelet aggregation (i.e., Aegyptin, apyrase, D7) represent functional redundancy. Our findings do not support this hypothesis; instead, they indicate that multiple salivary components work synergistically and are necessary to achieve maximum blood feeding efficiency.hematophagy | evolution | saliva | transgenesis | RNAi A edes aegypti, the main vector of dengue, chikungunya, and yellow fever viruses, is an anautogenous mosquito that requires a blood meal for egg development. Female mosquitoes probe the skin of a suitable vertebrate host to acquire a blood meal. Hematophagy (blood feeding) to repletion usually takes from seconds to a few minutes (1). The stylets used to pierce the vascular beds of the vertebrate hosts cause local damage that triggers host hemostatic responses.Primary hemostasis is characterized by vascular contraction, platelet adhesion, and formation of a soft aggregate plug that begins immediately after endothelial disruption. Injury causes temporary local contraction of vascular smooth muscle. Vasoconstriction slows blood flow, enhancing platelet adhesion and activation. The soft platelet plug is stabilized to form a clot during secondary hemostasis (2, 3). Hematophagic arthropods have evolved a complex mixture of salivary components that counteract platelet aggregation, blood coagulation, vasoconstriction, and inflammation to overcome this efficient and redundant vertebrate hemostatic system (4-6).Aedes aegypti, Anopheles stephensi, and Simulim nigrimanum express salivary collagen-binding proteins that prevent collagenin...

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Lundep, a Sand Fly Salivary Endonuclease Increases Leishmania Parasite Survival in Neutrophils and Inhibits XIIa Contact Activation in Human Plasma

Cited by 95 publications

References 36 publications

Exposure to Leishmania braziliensis Triggers Neutrophil Activation and Apoptosis

Exposure to Leishmania braziliensis Triggers Neutrophil Activation and Apoptosis

Cross-species genetic exchange between visceral and cutaneous strains of Leishmania in the sand fly vector

Collagen-binding protein, Aegyptin, regulates probing time and blood feeding success in the dengue vector mosquito, Aedes aegypti

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