An immune-responsive serpin, SRPN6, mediates mosquito defense against malaria parasites

被引:151
作者
Abraham, EG
Pinto, SB
Ghosh, A
Vanlandingham, DL
Budd, A
Higgs, S
Kafatos, FC
Jacobs-Lorena, M
Michel, K
机构
[1] European Mol Biol Lab, D-69117 Heidelberg, Germany
[2] Johns Hopkins Bloomberg Sch Publ Hlth, Malaria Res Inst, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA
[3] Univ London Imperial Coll Sci Technol & Med, Dept Biol Sci, London SW7 2AZ, England
[4] Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77550 USA
关键词
Anopheles; innate immunity; Plasmodium; midgut invasion; ookinete;
D O I
10.1073/pnas.0508335102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have functionally analyzed the orthologous SRPN6 genes from Anopheles stephensi and Anopheles gambiae using phylogenetic, molecular, reverse genetic, and cell biological tools. The results strongly implicate SRPN6 in the innate immune response against Plasmodium. This gene belongs to a mosquito-specific gene cluster including three additional Anopheles serpins. SRPN6 expression is induced by Escherichia coli and both rodent and human malaria parasites. The gene is specifically expressed in midgut cells invaded by Plasmodium ookinetes and in circulating and attached hemocytes. Knockdown of SRPN6 expression by RNA interference in susceptible An. stephensi leads to substantially increased parasite numbers, whereas depletion in susceptible An. gambiae delays progression of parasite lysis without affecting the number of developing parasites. However, the An. gambiae SRPN6 knockdown increases the number of melanized parasites in the L3-5 refractory strain and in susceptible G3 mosquitoes depleted of CTL4. These results indicate that AsSRPN6 is involved in the parasite-killing process, whereas AgSRPN6 acts on parasite clearance by inhibiting melanization and/or promoting parasite lysis. We propose that these observed phenotypic differences are due to changed roles of the respective target serine proteases in the two mosquito species.
引用
收藏
页码:16327 / 16332
页数:6
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