Parasitoid wasp venom SERCA regulates Drosophila calcium levels and inhibits cellular immunity

Nathan T. Mortimer, Jeremy Goecks, Balint Z. Kacsoh, James A. Mobley, Gregory J. Bowersock, James Taylor, Todd A. Schlenke

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Because parasite virulence factors target host immune responses, identification and functional characterization of these factors can provide insight into poorly understood host immune mechanisms. The fruit fly Drosophila melanogaster is a model system for understanding humoral innate immunity, but Drosophila cellular innate immune responses remain incompletely characterized. Fruit flies are regularly infected by parasitoid wasps in nature and, following infection, flies mount a cellular immune response culminating in the cellular encapsulation of the wasp egg. The mechanistic basis of this response is largely unknown, but wasps use a mixture of virulence proteins derived from the venom gland to suppress cellular encapsulation. To gain insight into the mechanisms underlying wasp virulence and fly cellular immunity, we used a joint transcriptomic/ proteomic approach to identify venom genes from Ganaspis sp.1 (G1), a previously uncharacterized Drosophila parasitoid species, and found that G1 venom contains a highly abundant sarco/endoplasmic reticulum calcium ATPase (SERCA) pump. Accordingly, we found thatflyimmune cells termed plasmatocytes normally undergo a cytoplasmic calciumburst following infection, and that this calcium burst is required for activation of the cellular immune response.We further found that the plasmatocyte calcium burst is suppressed by G1 venom in a SERCA-dependent manner, leading to the failure of plasmatocytes to become activated and migrate toward G1 eggs. Finally, by genetically manipulating plasmatocyte calcium levels, we were able to alter fly immune success against G1 and other parasitoid species. Our characterization of parasitoid wasp venom proteins led us to identify plasmatocyte cytoplasmic calcium bursts as an important aspect of fly cellular immunity.

Original languageEnglish (US)
Pages (from-to)9427-9432
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number23
DOIs
StatePublished - Jun 4 2013

ASJC Scopus subject areas

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