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PRESSRELEASE
“Daedalusdilemma”oftheimmunesystem
th
Vienna,March9 ,2016
Ourimmunesystemconstantlyfightsofbacteriaandvirusesandwhiledoingsoneedstofindacriticalbalance
betweenover-andunder-reaction,similartoDaedalusandIcarusinGreekmythologywhomustneitherflytoohigh
nortoolowtoescapetheircaptivity.Howthisbalancingactisregulatedatthemolecularlevelswassofarpoorly
understood.FirstinsightsarenowprovidedbyPavelKovarikandhisteamfromtheMaxF.PerutzLaboratoriesof
theUniversityofViennaandtheMedicalUniversityofVienna.Thegroupreportsthatinthedefenseagainstgroup
AStreptococci–bacteriathatcausetonsillitisbutalsoseriousandsometimesfatalinvasiveinfections–aperfectly
synchronizedinterplayoftwoimmunesubstancesiskey.ThemoleculesIL-1βandtypeIinterferoncontrolthe
strengthoftheimmuneresponsesimilartoarheostatthatvariestheresistanceinacircuit.Theresultsare
publishedinCellHost&Microbeandoffernewapproachestothetreatmentofseverestreptococcalinfections.
SimilaritiesbetweenGreekmythologyandtheimmunesystem
ThedilemmaofourimmunesystemiscomparabletothestoryofIcarusandDaedalusfromGreekmythology.To
escapetheircaptivity,Daedalusbuiltwingsfromfeathersandwaxforhimselfandhisson.Daedaluswarnedhisson
thathemustneitherflytoohighbutalsonottoolow,otherwisethesun'sheatorthehumidityoftheseawould
destroyhiswingsandhewouldcrash.Aftertheyhadsuccesfullyescaped,Icarusbecomeboisterousandflewhigher
andhigheruntilthesunbegantomeltthewaxofhiswingshefellintothesea.Similarly,anover-orunderreactionof
ourimmunesystemcanbelife-threatening.
ThemoleculeIL-1βplaysakeyroleinthebalanceddefenseagainstbacteria
Whicharethemoleculesthatensureabalancedimmuneresponse?TheresearchofPavelKovarikandhisteamatthe
MaxF.PerutzLaboratoriesoftheUniversityofViennaaddressesthisquestion."Forourexperimentswesimulated
infectionswithgroupAStreptococci,whicharebestknownasthecommoncauseoftonsillitis.However,insome
cases,theycanalsocauseseriousinvasiveinfections.Therelateddisease–toxicshocksyndromeandnecrotizing
fasciitis–canbefatal,"explainsPhDstudentandfirstauthorofthestudyVirginiaCastiglia.Aspartofaprojectfunded
bytheAustrianScienceFundFWFproject,theyoungscientistexaminedwhathappensatthemolecularlevelin
invasivestreptococcalinfection.HerresultsshowthatthemoleculeIL-1βplayakeyroleinthedefenseagainst
streptococci:ifthereistoolittle,thebacteriagaintheupperhandfollowedbybloodpoisoning,ifthereistoomuch,
theresultisexcessiveinflammation.Bothcanbelethal.
Tippingthescales:typeIinterferons
ButhowistheamountofIL-1βregulated?"WecouldshowthattypeIinterferons(IFN-I)arekey,"saysstudylead
PavelKovarik:"WehaveknownforalongtimethatIFN-Ihelpsinthefightagainstviruses,buttheirroleinthe
defenseagainstbacteriawasfarlessclear.Forthefirsttime,wecouldnowshowinourmodelsystemthattheyalso
playanimportantroleinbacterialinfectionstoobyreducingtheamountofIL-1βandsopreventingexcessive
inflammation."
Newtherapiestotreatinvasivestreptococcaldisease
Theseresultsshouldnowpromptmedicalresearchasitisimportanttounderstand,besidesthemodelsystem,how
theamountofIL-1βisbalancedinpatientsandhowitisrelatedtotheseverityoftheinfection.VirginiaCastiglia
MAXF.PERUTZLABORATORIES
ViennaBiocenter(VBC,)Dr.Bohr-Gasse9|1030Wien|Austria
Tel:+431427724014
[email protected]|www.mfpl.ac.at
TheMaxF.PerutzLaboratoriesareajointventureof
PRESSRELEASE
explains:"InourmodelwehaveshownthatifIFN-Ieffectsarereduced,treatmentwithinhibitorsofIL-1βsynthesis
havepositiveeffectsandbalanceisrestored.OnceweunderstandtherelationshipbetweenIFN-IandIL-1βin
humans,wecantesttheseandsimilartherapies."Untilnow,seriousinvasivestreptococcalinfectioncanonlybe
treatedsymptomatically.Antibioticsonlyhelpintheearlystagesandanti-inflammatoryagentsshowlittleeffect.
Oftentheonlywayisthegenerousremovaloftheinflamedtissue.SothereisstillalottodoforPavelKovarikandhis
team.VirginiaCastigliaalsocontinuestoaddressquestionsrelatedtoinfectionbiology.Sincemid-February,sheisa
PostdocattheInstitutPasteurinParis,fundedbyprestigiousaMarieCuriegrantfromtheEuropeanUnion.
PublicationinCellHost&Microbe:
VirginiaCastiglia,AlessandraPiersigilli,FlorianEbner,MartonJanos,OliverGoldmann,UrsulaDamböck,Andrea
Kröger,SigfriedWeiss,SylviaKnapp,AmandaM.Jamieson,CarstenKirschning,UlrichKalinke,BirgitStrobl,Mathias
Müller,DagmarStoiber,StefanLienenklaus&PavelKovarik:TypeIInterferonSignalingPreventsIL-1bDrivenLethal
SystemicHyperinflammationduringInvasiveBacterialInfectionofSoftTissue.In:CellHost&Microbe(March2016)
DOI:http://dx.doi.org/10.1016/j.chom.2016.02.003
OnlinePressRelease:
http://www.mfpl.ac.at/about-us/press-media-info/pressdetail/news-detail/daedalus-dilemma-of-the-immunesystem.html
Presscontact
Dr.LillySommer
MaxF.PerutzLaboratories
Communications
T+43-1-4277-24014
[email protected]
TheMaxF.PerutzLaboratories(MFPL)areacenterestablishedbytheUniversityofViennaandtheMedicalUniversity
ofViennatoprovideanenvironmentforexcellent,internationallyrecognizedresearchandeducationinthefieldof
MolecularBiology.Onaverage,theMFPLhost60independentresearchgroups,involvingmorethan500peoplefrom
40nations.
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