1. Immunomodulation by Mosquito Salivary Protein AgSAP Contributes to Early Host Infection by Plasmodium
- Author
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Gunjan Arora, Andaleeb Sajid, Yu-Min Chuang, Yuemei Dong, Akash Gupta, Kristen Gambardella, Kathleen DePonte, Lionel Almeras, George Dimopolous, Erol Fikrig, Yale University [New Haven], Johns Hopkins University School of Medicine [Baltimore], Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), and Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille)
- Subjects
Plasmodium berghei ,Plasmodium falciparum ,malaria ,mosquito ,Mosquito Vectors ,Microbiology ,Mice ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Virology ,Anopheles ,parasitic diseases ,Animals ,Humans ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,Salivary Proteins and Peptides ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,immune regulation ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,QR1-502 ,Mice, Inbred C57BL ,stomatognathic diseases ,Sporozoites ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Insect Proteins ,Female ,Research Article - Abstract
Malaria is caused when Plasmodium sporozoites are injected along with saliva by an anopheline mosquito into the dermis of a vertebrate host. Arthropod saliva has pleiotropic effects that can influence local host responses, pathogen transmission, and exacerbation of the disease. A mass spectrometry screen identified mosquito salivary proteins that are associated with Plasmodium sporozoites during saliva secretions. In this study, we demonstrate that one of these salivary antigens, Anopheles gambiae sporozoite-associated protein (AgSAP), interacts directly with Plasmodium falciparum and Plasmodium berghei sporozoites. AgSAP binds to heparan sulfate and inhibits local inflammatory responses in the skin. The silencing of AgSAP in mosquitoes reduces their ability to effectively transmit sporozoites to mice. Moreover, immunization with AgSAP decreases the Plasmodium burden in mice that are bitten by Plasmodium-infected mosquitoes. These data suggest that AgSAP facilitates early Plasmodium infection in the vertebrate host and serves as a target for the prevention of malaria. IMPORTANCE Malaria is a vector-borne disease caused by Plasmodium sporozoites. When an anopheline mosquito bites its host, it releases Plasmodium sporozoites as well as saliva components. Mosquito proteins have the potential to serve as antigens to prevent or influence malaria without directly targeting the pathogen. This may help set a new paradigm for vaccine development. In this study, we have elucidated the role of a novel salivary antigen, named Anopheles gambiae sporozoite-associated protein (AgSAP). The results presented here show that AgSAP interacts with Plasmodium falciparum and Plasmodium berghei sporozoites and modulates local inflammatory responses in the skin. Furthermore, our results show that AgSAP is a novel mosquito salivary antigen that influences the early stages of Plasmodium infection in the vertebrate host. Individuals living in countries where malaria is endemic generate antibodies against AgSAP, which indicates that AgSAP can serve as a biomarker for disease prevalence and epidemiological analysis.
- Published
- 2021
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