The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B
Saliva of the blood feeding sand fly Lutzomyia longipalpis was previously shown to inhibit the alternative pathway (AP) of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin inhibited the deposition of C3b, Bb, Properdin, C5b,...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-08-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01065/full |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Antonio F. Mendes-Sousa Antonio F. Mendes-Sousa Vladimir Fazito do Vale Vladimir Fazito do Vale Naylene C. S. Silva Anderson B. Guimaraes-Costa Marcos H. Pereira Marcos H. Pereira Mauricio R. V. Sant’Anna Mauricio R. V. Sant’Anna Fabiano Oliveira Shaden Kamhawi José M. C. Ribeiro John F. Andersen Jesus G. Valenzuela Ricardo N. Araujo Ricardo N. Araujo |
| spellingShingle |
Antonio F. Mendes-Sousa Antonio F. Mendes-Sousa Vladimir Fazito do Vale Vladimir Fazito do Vale Naylene C. S. Silva Anderson B. Guimaraes-Costa Marcos H. Pereira Marcos H. Pereira Mauricio R. V. Sant’Anna Mauricio R. V. Sant’Anna Fabiano Oliveira Shaden Kamhawi José M. C. Ribeiro John F. Andersen Jesus G. Valenzuela Ricardo N. Araujo Ricardo N. Araujo The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B Frontiers in Immunology sand fly saliva Lufaxin complement system inhibition alternative pathway |
| author_facet |
Antonio F. Mendes-Sousa Antonio F. Mendes-Sousa Vladimir Fazito do Vale Vladimir Fazito do Vale Naylene C. S. Silva Anderson B. Guimaraes-Costa Marcos H. Pereira Marcos H. Pereira Mauricio R. V. Sant’Anna Mauricio R. V. Sant’Anna Fabiano Oliveira Shaden Kamhawi José M. C. Ribeiro John F. Andersen Jesus G. Valenzuela Ricardo N. Araujo Ricardo N. Araujo |
| author_sort |
Antonio F. Mendes-Sousa |
| title |
The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B |
| title_short |
The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B |
| title_full |
The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B |
| title_fullStr |
The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B |
| title_full_unstemmed |
The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B |
| title_sort |
sand fly salivary protein lufaxin inhibits the early steps of the alternative pathway of complement by direct binding to the proconvertase c3b-b |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Immunology |
| issn |
1664-3224 |
| publishDate |
2017-08-01 |
| description |
Saliva of the blood feeding sand fly Lutzomyia longipalpis was previously shown to inhibit the alternative pathway (AP) of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin inhibited the deposition of C3b, Bb, Properdin, C5b, and C9b on agarose-coated plates in a dose-dependent manner. It also inhibited the activation of factor B in normal serum, but had no effect on the components of the membrane attack complex. Surface plasmon resonance (SPR) experiments demonstrated that Lufaxin stabilizes the C3b-B proconvertase complex when passed over a C3b surface in combination with factor B. Lufaxin was also shown to inhibit the activation of factor B by factor D in a reconstituted C3b-B, but did not inhibit the activation of C3 by reconstituted C3b-Bb. Proconvertase stabilization does not require the presence of divalent cations, but addition of Ni2+ increases the stability of complexes formed on SPR surfaces. Stabilization of the C3b-B complex to prevent C3 convertase formation (C3b-Bb formation) is a novel mechanism that differs from previously described strategies used by other organisms to inhibit the AP of the host complement system. |
| topic |
sand fly saliva Lufaxin complement system inhibition alternative pathway |
| url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.01065/full |
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doaj-62f679289333404d9f3a5edfbda1bda22020-11-24T23:56:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-08-01810.3389/fimmu.2017.01065286260The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-BAntonio F. Mendes-Sousa0Antonio F. Mendes-Sousa1Vladimir Fazito do Vale2Vladimir Fazito do Vale3Naylene C. S. Silva4Anderson B. Guimaraes-Costa5Marcos H. Pereira6Marcos H. Pereira7Mauricio R. V. Sant’Anna8Mauricio R. V. Sant’Anna9Fabiano Oliveira10Shaden Kamhawi11José M. C. Ribeiro12John F. Andersen13Jesus G. Valenzuela14Ricardo N. Araujo15Ricardo N. Araujo16Physiology of Hematophagous Insects Laboratory, Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilCampus Senador Helvídio Nunes de Barros, Universidade Federal do Piauí, Picos, Piauí, BrazilPhysiology of Hematophagous Insects Laboratory, Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilLaboratory of Simuliids and Onchocerciasis, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Rio de Janeiro, BrazilPhysiology of Hematophagous Insects Laboratory, Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilVector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United StatesPhysiology of Hematophagous Insects Laboratory, Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilInstituto Nacional de Ciência e Tecnologia em Entomologia Molecular, Rio de Janeiro, Rio de Janeiro, BrazilPhysiology of Hematophagous Insects Laboratory, Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilInstituto Nacional de Ciência e Tecnologia em Entomologia Molecular, Rio de Janeiro, Rio de Janeiro, BrazilVector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United StatesVector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United StatesVector Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United StatesVector Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United StatesVector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United StatesPhysiology of Hematophagous Insects Laboratory, Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilInstituto Nacional de Ciência e Tecnologia em Entomologia Molecular, Rio de Janeiro, Rio de Janeiro, BrazilSaliva of the blood feeding sand fly Lutzomyia longipalpis was previously shown to inhibit the alternative pathway (AP) of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin inhibited the deposition of C3b, Bb, Properdin, C5b, and C9b on agarose-coated plates in a dose-dependent manner. It also inhibited the activation of factor B in normal serum, but had no effect on the components of the membrane attack complex. Surface plasmon resonance (SPR) experiments demonstrated that Lufaxin stabilizes the C3b-B proconvertase complex when passed over a C3b surface in combination with factor B. Lufaxin was also shown to inhibit the activation of factor B by factor D in a reconstituted C3b-B, but did not inhibit the activation of C3 by reconstituted C3b-Bb. Proconvertase stabilization does not require the presence of divalent cations, but addition of Ni2+ increases the stability of complexes formed on SPR surfaces. Stabilization of the C3b-B complex to prevent C3 convertase formation (C3b-Bb formation) is a novel mechanism that differs from previously described strategies used by other organisms to inhibit the AP of the host complement system.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01065/fullsand flysalivaLufaxincomplement system inhibitionalternative pathway |