Multifunctionality and mechanism of ligand binding in a mosquito antiinflammatory protein

Calvo, Eric; Mans, Ben J.; Ribeiro, José M. C.; Andersen, John F.

doi:10.1073/pnas.0813190106

Cited by 126 publications

(192 citation statements)

References 34 publications

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“…Removal of ATP and ADP from the biting site reduces the pain cause by these extracellular nucleotides and limits their effect on platelet activation. In contrast, the D7 protein, a multifunctional molecule found in mosquitoes, serves the important functions of inhibiting platelet aggregation, vasoconstriction, inflammation, and host behavioral responses that might disturb feeding (27)(28)(29)(30)(31)(32).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…In addition, GSG6 was found to be a serological indicator of exposure to Afrotropical malaria vectors [37]. The D7 short proteins bind serotonin with high affinity, as well as histamine and norepinephrine, thus antagonizing the vasoconstrictor, platelet-aggregating, and paininducing level of these factors [38]. gVAG is a defense-related protein [39].…”

Section: Wwwintechopencommentioning

confidence: 99%

Proteomics of Anopheles gambiae

Choumet¹

2012

Malaria Parasites

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“…Aed a 2 contains an N-terminal and a C-terminal domain, capable of binding to leukotrienes and biogenic amines that are released by an individual as a mechanism of defense against the mosquito bite [76]. The gene encoding this protein was first identified in a cDNA library constructed from the salivary glands of A. aegypti .…”

Section: Mosquito Allergensmentioning

confidence: 99%

Immunological Aspects of the Immune Response Induced by Mosquito Allergens

Cantillo

Fernández-Caldas

Puerta

2014

Int Arch Allergy Immunol

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Allergies caused by mosquito bites may produce local or systemic reactions. The inhalation of mosquito allergens may also cause asthma and/or allergic rhinoconjunctivitis in sensitized individuals. The mechanisms implicated in the development of these immune responses involve IgE antibodies, different subtypes of IgG and proinflammatory cytokines as well as basophils, eosinophils and mast cells. Several allergenic components have been identified in the saliva and bodies of mosquitoes and some of these are present in different mosquito species. The most common species implicated in allergic reactions belong to the genera Aedes, Culex and Anopheles. Several Aedes aegypti allergens have been cloned and sequenced. The recombinant molecules show IgE reactivity similar to that of the native allergens, making them good candidates for the diagnosis of mosquito allergies. Allergen-specific immunotherapy with mosquito extracts induces a protective response characterized by a decreased production of IgE antibodies, increased IgG levels, a reduction in the severity of cutaneous and respiratory symptoms and the need for medication. The aims of this review are to summarize the progress made in the characterization of mosquito allergens and discuss the types of immune responses induced by mosquito bites and the inhalation of mosquito allergens in atopic individuals.

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Multifunctionality and mechanism of ligand binding in a mosquito antiinflammatory protein

Abstract: biogenic amine ͉ bloodfeeding ͉ leukotriene ͉ odorant-binding protein ͉ saliva

Cited by 126 publications

References 34 publications

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

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

Proteomics of Anopheles gambiae

Immunological Aspects of the Immune Response Induced by Mosquito Allergens

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