Grants and Contracts Details
Among metazoa, innate immunity is a conserved, robust, and complex phenomenon involving both cellular and humoral response elements. Recently independent results from our two labs made it apparent that the NF-Kj3 cell signaling pathways, which are known to regulate important aspects of embryonic development and antibacterial immune responses may also regulate cellular immune responses to endoparasitic wasps. Presently, we have a substantial understanding of the molecular mechanisms involved in Drosophila antibacterial and anti-fungal immunity. However, molecular characteristics of insect cellular immune responses remain largely unresolved. Parasitoids attacking both Diptera and Lepidoptera have evolved means to subvert or block the immune responses via polydnaviruses (e.g. PDVs of ichneumonid and braconid wasps that attack many lepidopteran species) or virus like particles (e.g. VLPs of the wasp Leptopilina that infect Drosophila). Recent genome sequence analysis in the Webb laboratory of 5 PDV genomes, representing the major PDV groups has revealed that members of only one gene family is encoded in all seven sequenced genomes. These genes encode proteins with ankyrin repeats, similar to those found in the IKB-family of proteins, that normally inhibit NF-KB signaling in Drosophila and vertebrate cells by sequestering the NF-KB transcription factors. Significantly, the viral ankyrin (vanJ.yrin) genes are differentially expressed in immune cells (hemocytes and fat body) after the host is infected. Vankyrin proteins lack the regulatory domains typical of other IKj3proteins suggesting that vankyrin proteins may function as dominant negative mutants that block host immune responses by interfering with NFKj3- dependent signaling. The discovery of functional vankyrin genes in diverse PDV genomes may indicate that NF-KB signaling is indeed activated in insects when they are infected by parasitoids. Genome-wide expression analysis of Drosophila larval hosts infected with non-virulent wasps performed in the Govind lab supports this very idea. Here we propose to combine the power of Drosophila genetics and biochemical/molecular approaches of lepidopteran systems to test if NF-KB signaling is also central to host defense against macrosc~pic pathog~ns. We propose to: 1) determine whether similar expression patterns occur in Lepidoptera upon ImmunologIcal challenge by avirulent and virulent parasitoids; and (2) determine whether expression of vankyrin family genes can turn off immunity pathways in lepidopteran and Drosophila cells and larvae, and whether expression of fly NF-KB genes and mutants thereof can regulate NF-KB signaling in lepidopteran cells. Our work will contribute to a more complete understanding of innate immunity and virulence mechanisms in diverse insects with potential applications to the control of economically-important pests.
|Effective start/end date||1/15/07 → 1/14/10|
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