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.
Highlights
Mosquitoes can transmit important parasitic diseases such as malaria and filariasis and viral diseases such as yellow fever, dengue, Rift Valley fever and the West Nile virus
Ingested blood contains bioactive molecules belonging to the innate immune defense mechanisms against microbes, like the complement system, that can damage foreign cells
We have identified in this study a mechanism whereby mosquitoes can escape the damaging activity of the complement system in the ingested human blood
Summary
Mosquitoes can transmit important parasitic diseases such as malaria and filariasis and viral diseases such as yellow fever, dengue, Rift Valley fever and the West Nile virus. Aedes, Culex, Coquillettidia, Mansonia and Ochlerotatus species are the best known disease transmitting mosquitoes[1]. They all require a blood meal to obtain proteins from their hosts. Ingestion of host blood has been suggested to pose a danger to mosquitoes as a result of exposing the alimentary canal (AC) to bioactive molecules that normally exist in host blood as part of the host defense mechanisms against microbes. Other ingested blood-derived factors such as antibodies, hemoglobin-derived peptides, enzymes and signaling molecules could alter the physiology of hematophagous vectors (reviewed in[2]). The most immediate system that has been shown to be overcome by mosquitoes and other hematophagous vectors is the coagulation system[3]. The injected saliva contained anti-coagulants that permitted smooth flow of blood from the skin of the host to the vector and prevented blockage of the blood sucking capillary[3]
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