Evidence of an Antimicrobial-Immunomodulatory Role of Atlantic Salmon Cathelicidins during Infection with Yersinia ruckeri 英文参考文献.docVIP

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Evidence of an Antimicrobial-Immunomodulatory Role of Atlantic Salmon Cathelicidins during Infection with Yersinia ruckeri 英文参考文献.doc

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Evidence of an Antimicrobial-Immunomodulatory Role of Atlantic Salmon Cathelicidins during Infection with Yersinia ruckeri 英文参考文献

EvidenceofanAntimicrobial-ImmunomodulatoryRoleof AtlanticSalmonCathelicidinsduringInfectionwith Yersiniaruckeri AndrewBridle*,ElizabethNosworthy,MarkPolinski,BarbaraNowak NationalCentreforMarineConservationandResourceSustainability,UniversityofTasmania,Tasmania,Australia Abstract Cathelicidinsareafamilyofantimicrobialpeptidesthatactaseffectormoleculesoftheinnateimmunesystemwithbroad- spectrumantimicrobialproperties.Theseevolutionaryconservedcationichost-defencepeptidesareintegralcomponents of the immune response of fish, which are generally believed to rely heavily on innate immune defences to invading pathogens.InthisstudyweshowedthatAtlanticsalmoncathelicidin1and2(asCATH1andasCATH2)stimulatedperipheral bloodleukocytesincreasingthetranscriptionofthechemokineinterleukin-8.Further,functionaldifferenceswereidentified betweenthetwocathelicidins.Inthepresenceofserum,asCATH1displayedgreatlydiminishedhosthaemolyticactivity, whiletheconstitutivelyexpressedasCATH2hadnohaemolyticactivitywithorwithoutserum.Thesefindingssupportour hypothesisthatfishcathelicidinsexerttheirprimaryantimicrobialactionatthesiteofpathogeninvasionsuchasepithelial surfaces.Further,wehypothesisethatliketheirmammaliancounterpartsinthepresenceofserumtheyactasmediatorsof the innate and adaptive immune response via the release of cytokines thus indirectly protecting against a variety of pathogens. We highlight the importance of this immunomodulatory role from the involvement of asCATHs during an infectionwiththefishpathogenYersiniaruckeri.WhilewewereabletodemonstrateinvitrothatasCATH1and2,possessed direct microbicidal activity against the fish pathogen, Vibrio anguillarum, and a common gram negative bacterium, Escherichia coli, little or no bactericidal activity was found against Y. ruckeri. The contribution of either asCATH in the immune response or as a potential virulence factor during yersiniosis is highlighted from the increased expression of asCATH1and2mRNAduringaninvivochallengewithY.ruckeri.Wepro