Open AccessA genetic module regulates the melanization response of Anopheles to Plasmodium
Author(s) -
Volz Jennifer,
Müller HansMichael,
Zdanowicz Agnieszka,
Kafatos Fotis C.,
Osta Mike A.
Publication year - 2006
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2006.00718.x
Subject(s) - biology , gene knockdown , anopheles gambiae , plasmodium (life cycle) , proteases , rna interference , gene , immune system , anopheles , phenotype , vector (molecular biology) , transcriptome , serine protease , genetics , microbiology and biotechnology , virology , parasite hosting , malaria , protease , rna , immunology , gene expression , biochemistry , world wide web , computer science , enzyme , recombinant dna
Summary Two modes of refractoriness to Plasmodium , ookinete lysis and melanization, are known in the malaria vector, Anopheles gambiae . Melanization, a potent insect immune response, is manifested in a genetically selected refractory strain and in susceptible mosquitoes that are depleted of specific C‐type lectins (CTLs). Here we use a systematic in vivo RNA interference‐mediated reverse genetic screen and other recent results to define a melanization‐regulating genetic module or network. It encompasses at least 14 genes, including those that encode five Easter‐like clip domain serine proteases and four Masquerade‐like serine protease homologues of the mosquito CLIPB and CLIPA subfamilies respectively. We show that several but not all CLIPB genes promote Plasmodium melanization, exhibiting partial functional overlap and synergy. We also report that several CLIPA genes have contrasting roles: CLIPA8 is essential for parasite melanization, while three other CLIPAs are novel synergistic inhibitors of this response. Importantly, the roles of certain CLIPAs and CLIPBs are strain specific, indicating that this network may differ between strains. Finally, we provide evidence that in susceptible mosquitoes melanization induced by knockdown of either CTL4 or CLIPA2/CLIPA5 directly kills ookinetes, in contrast to refractory mosquitoes where it merely disposes of dead parasites.