The Sand Fly Salivary Protein Lufaxin Inhibits the Early Steps of the Alternative Pathway of Complement by Direct Binding to the Proconvertase C3b-B

Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Laboratório de Fisiologia de Insetos Hematófagos. Belo Horizonte, MG, Brasil / Universidade Federal do Piauí. Campus Senador Helvídio Nunes de Barros. Picos, PI, Brasil
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Laboratório de Fisiologia de Insetos Hematófagos. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Simulídeos, Oncocercose e Infecções Simpátricas: Mansonelose e Malária. Rio de Janeiro, RJ, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Laboratório de Fisiologia de Insetos Hematófagos. Belo Horizonte, MG, Brasil.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Vector Molecular Biology Section. Rockville, MD, USA.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Laboratório de Fisiologia de Insetos Hematófagos. Belo Horizonte, MG, Brasil / Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular. Rio de Janeiro,RJ, Brasil.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Laboratório de Fisiologia de Insetos Hematófagos. Belo Horizonte, MG, Brasil / Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular. Rio de Janeiro,RJ, Brasil.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Vector Molecular Biology Section. Rockville, MD, USA.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Vector Molecular Biology Section. Rockville, MD, USA.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Vector Molecular Biology Section. Rockville, MD, USA.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Vector Molecular Biology Section. Rockville, MD, USA.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Vector Molecular Biology Section. Rockville, MD, USA.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Laboratório de Fisiologia de Insetos Hematófagos. Belo Horizonte, MG, Brasil / Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular. Rio de Janeiro,RJ, Brasil.

Abstract

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 Ni(2+) 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.

Keywords in Portuguese

Psychodidae
Saliva
caminho alternativo
inibição do sistema de complemento
Lufaxin

Keywords

sand fly
saliva
Lufaxin
complement system inhibition
alternative pathway

Publisher

Frontiers Media

Citation

SOUSA, Antonio F. Mendes; et al. 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, v.8, Article 1065, 12p, Aug. 2017.

DOI

10.3389/fimmu.2017.01065

ISSN

1664-3224

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/23154

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