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Peptidogyclan recognition proteins at the intersection of innate immunity and animal development in the squid/Vibrio symbiosis

Posted on:2010-03-12Degree:Ph.DType:Dissertation
University:The University of Wisconsin - MadisonCandidate:Troll, Joshua VFull Text:PDF
Symbiotic associations with beneficial bacteria are ubiquitous throughout the animal kingdom. However, little is understood about the molecular 'dialog' underlying the initiation and maintenance of mutualistic associations. Recent studies of the symbiosis between the Hawaiian bobtail squid Euprymna scolopes and the luminous Gram-negative bacterium Vibrio fischeri have implicated the host immune system as an important mediator of interactions with the symbiont. Peptidoglycan (PGN) monomers released by V. fischeri irreversibly trigger development of the light organ - the host structure which houses the symbiont. Peptidoglycan recognition proteins are a family of animal innate immunity proteins that mediate host responses to PGN. I identified and characterized four PGRPs expressed in the E. scolopes light organ, EsPGRP1-4. EsPGRP1 was found to be an intranuclear protein. The nuclear localization of EsPGRP1 was lost, prior to DNA breakdown (TUNEL), during the apoptotic program associated with light-organ development. Both of these responses were triggered by treatment with PGN-monomers. The loss of EsPGRP1 and subsequent TUNEL staining was used as an assay to assign a morphogenetic activity to symbiont bioluminescence. The host response to symbiotic illumination was specific to blue light and was blocked by pharmacologically increasing cGMP levels in the host tissues, suggesting that bioluminescence acts through a host phototransduction cascade. Finally, EsPGRP2 was secreted from epithelial surfaces and was determined to enzymatically cleave and inactivate PGN monomers. Thus, EsPGRP2 modulates the signaling activity of PGN-derived signals from the bacterial symbiont.
Keywords/Search Tags:PGN, Proteins, Development, Symbiont
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