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

Eappen G. Abraham, Sofia B. Pinto, Anil Ghosh, Dana L. Vanlandingham, Aidan Budd, Stephen Higgs, Fotis C. Kafatos, Marcelo Jacobs-Lorena, Kristin Michel

Research output: Contribution to journalArticlepeer-review

Abstract

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. gamblae 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.

Original languageEnglish (US)
Pages (from-to)16327-16332
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number45
DOIs
StatePublished - Nov 8 2005

Keywords

  • Anopheles
  • Innate immunity
  • Midgut invasion
  • Ookinete
  • Plasmodium

ASJC Scopus subject areas

  • General

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