Abstract
Malaria is a worldwide health problem that affects two-thirds of the world population. Plasmodium invasion of anopheline mosquitoes is an obligatory step for malaria transmission. However, mosquito-malaria molecular interactions in nature are not clear. A genetic variation within mosquito fibrinogen related-protein 30 (FBN30) was previously identified to be associated with Plasmodium falciparum infection in natural Anopheles gambiae populations at malaria endemic areas in Kenya, and reducing FBN30 expression by RNAi makes mosquitoes more susceptible to P. berghei. New results show that FBN30 is a secreted octamer that binds to both P. berghei and clinically circulating P. falciparum from malaria endemic areas in Kenya, but not laboratory P. falciparum strain NF54. Moreover, the natural genetic mutation (T to C) within FBN30 signal peptide, which changes the position 10 amino acid from phenylalanine to leucine, reduces protein expression by approximately half. This change is consistent to more susceptible An. gambiae to P. falciparum infection in the field. FBN30 in natural An. gambiae is proposed to work as a pathogen recognition molecule in inhibiting P. falciparum transmission in malaria endemic areas.
Highlights
Mosquitoes transmit many human diseases such as malaria, dengue fever, and Zika
Using enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assays (IFA), we found that fibrinogen related-protein 30 (FBN30) is able to interact with P. berghei and clinically circulating P. falciparum isolates, but not with laboratory P. falciparum strain NF54
Non-self-recognition by FREPs functioning as pathogen recognition receptors (PRRs) to initiate innate immunity against pathogens has been described in several invertebrate species[4]
Summary
Mosquitoes transmit many human diseases such as malaria, dengue fever, and Zika. Due to absence of adaptive immunity, mosquitoes rely on innate immunity to mount a defense against these pathogens. The family of fibrinogen-related proteins (FREPs, known as fibrinogen domain immunolectins or FBNs) is reportedly involved in innate immunity against malaria and other pathogens[1]. FBNs have been identified from a wide range of species functioning as pattern-recognition receptors (PRRs) through the binding of carbohydrates on the outer membrane pathogens. Mosquito FBN30 is proposed to be a pathogen recognition molecule against clinically circulating P. falciparum infection in natural An. gambiae populations in malaria endemic areas in Kenya. This molecule could be used as a target by small molecules to reduce malaria burden
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