title: Anopheles midgut epithelium evades human complement activity by capturing factor H from the blood meal.
abstract: Hematophagous vectors strictly require ingesting blood from their hosts to complete their life cycles. Exposure of the alimentary canal of these vectors to the host immune effectors necessitates efficient counteractive measures by hematophagous vectors. The Anopheles mosquito transmitting the malaria parasite is an example of hematophagous vectors that within seconds can ingest human blood double its weight. The innate immune defense mechanisms, like the complement system, in the human blood should thereby immediately react against foreign cells in the mosquito midgut. A prerequisite for complement activation is that the target cells lack complement regulators on their surfaces. In this work, we analyzed whether human complement is active in the mosquito midgut, and how the mosquito midgut cells protect themselves against complement attack. We found that complement remained active for a considerable time and was able to kill microbes within the mosquito midgut. However, the Anopheles mosquito midgut cells were not injured. These cells were found to protect themselves by capturing factor H, the main soluble inhibitor of the alternative complement pathway. Factor H inhibited complement on the midgut cells by promoting inactivation of C3b to iC3b and preventing the activity of the alternative pathway amplification C3 convertase enzyme. An interference of the FH regulatory activity by monoclonal antibodies, carried to the midgut via blood, resulted in increased mosquito mortality and reduced fecundity. By using a ligand blotting assay, a putative mosquito midgut FH receptor could be detected. Thereby, we have identified a novel mechanism whereby mosquitoes can tolerate human blood.
authors: Research Program Unit, Immunobiology Research Program, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors: Ayman
authors: A
authors: Khattab
authors: Research Program Unit, Immunobiology Research Program, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors: Marta
authors: M
authors: Barroso
authors: Research Program Unit, Immunobiology Research Program, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors: Tiera
authors: T
authors: Miettinen
authors: Research Program Unit, Immunobiology Research Program, Haartman Institute, University of Helsinki, Helsinki, Finland; Helsinki University Central Hospital, Helsinki, Finland.
authors: Seppo
authors: S
authors: Meri
mesh_terms: D000818:Animals; D000852:Anopheles / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D003167:Complement Activation / Q000276:immunology*; D050577:Complement C3-C5 Convertases / Q000096:biosynthesis / Q000276:immunology; D003179:Complement C3b / Q000276:immunology; D017242:Complement Factor H / Q000276:immunology*; D004064:Digestive System / Q000276:immunology; D006801:Humans; D057131:Immune Evasion / Q000276:immunology*; D007303:Insect Vectors / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000469:parasitology; D008018:Life Cycle Stages; D011951:Receptors, Complement / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D011951:Receptors, Complement; C044257:factor H receptors; D003179:Complement C3b; D017242:Complement Factor H; D050577:Complement C3-C5 Convertases