文档介绍：该【Zone defence – the gut microbiota position macrophages for optimal liver protection 2021 Kieran English 】是由【琪官】上传分享，文档一共【5】页，该文档可以免费在线阅读，需要了解更多关于【Zone defence – the gut microbiota position macrophages for optimal liver protection 2021 Kieran English 】的内容，可以使用淘豆网的站内搜索功能，选择自己适合的文档，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此文档到您的设备，方便您编辑和打印。Immunology&CellBiology2021;1–5
NEWSANDCOMMENTARY
Zonedefence–thegutmicrobiotapositionmacrophages
foroptimalliverprotection
KieranEnglish,DavidGBowen&PatrickBertolino
CentenaryInstituteandAWMorrowGastroenterologyandLiverCentre,UniversityofSydneyandRoyalPrinceAlfredHospital,Sydney,
NSW,Australia
Immunology&CellBiology2021;1–5;doi:
Theliveristhelargestinternalorgansinusoids,wheretheyinteractwithroleofKupffercellswithinthe
-bothLSECsandhepatocytes,
thirdsofitsbloodflowissuppliedatthesametimebeingexposedtoadditionallevelofcomplexitytothis
Throughitsdirectbloodsupplysamplepathogens,microbialanunlikelycoachingteam
fromthegut,andthelargevisceralproducts,andfoodantigensfrominstructingKCstopreferentially
surfaceborderingtheperitonealthegut,andareconsideredoneoflocalizeintheperiportalregion,
cavity,theliveristhetargetofthekeysentinelsoftheliver,playingclosesttotheportalinflow,creating
severalpathogensthatcanessentialrolesinpathogenclearanceaKCdistributiongradientoptimized
,4forefficientimmunesurveillance.
,KCswereThesenewfindingssuggestthatboth
context,itisnotsurprisingthatliverconsideredthesolepopulationoffunctionandlocationofKCsare
.
,wehaverecentlyidentifiedThefunctionalrelevanceofthis
PreventingthedisseminationofanotherphenotypicallydistinctliverunevenKCdistribution,whichthe
bloodbornepathogensisoneoftheresidentmacrophagesubsetauthorstermed“immunezonation”,
maintasksofKupffercells(KCs),positionedatthesecondpotentialcanbemoreeasilycomprehendedin
thelargestpopulationofresidentsiteofpathogenentry:theliverthecontextofthearchitectureand
resideinnarrowhepaticcapillaries,macrophages(LCMs)areanchoredplayingfield:
knownassinusoids,whereportaltocollagenfiberscontainedintheparenchymaisclassicallyorganized
andarterialbloodmixandpercolatecapsuleandformacontiguousasrepeatinghexagonalunitsknown
beforeexitingviacentralveinscellularnetwork(Figure1).Inaslobules(Figure1).Thecenterof
(Figure1).ThehepaticsinusoidsarecontrasttoKCsthatarethelobuleisdefinedbyonecentral
delimitedbysinglelayersofliverembryonicallyderived,LCMsareveinwhileeachpointofthehexagon
parenchymalcells(hepatocytes),andderivedfrombloodmonocytesandcorrespondstoavascularstructure,
,thatcontains
fenestratedendothelialcellsknownLCMsareabletosensebacteriaaportalvein,ahepaticartery,anda
(LSECs)possessingunusualimmuneperitonealcavityandrecruitsinusoidsfromtheportaltriadsto
,twopreviouslyestablishedthatKCsare
populationsofresidentmacrophagephenotypicallyheterogeneousand
Correspondenceactassentinelswithintheliver:notevenlydistributedwithinthe
PatrickBertolino,CentenaryInstituteandLCMsguardtheouterlimitsoftheliverlobule,withperiportalareas
AWMorrowGastroenterologyandLiverliverfromtheperitonealcavityandcontainingtwo-foldmoreKCsthan
Centre,UniversityofSydneyandRoyal
PrinceAlfredHospital,LockedBag#6,
Newtown,NSW2042,,Golatheseobservationsweremade
6
E-mail:p.******@,themechanisms
1
MicrobiotaoptimiseKupffercellfunctionKEnglishetal.
-
betweentheliverparenchymaandKupffercellssituatedwithintheliversinusoidsprotecttheliverfrompathogensenteringviatheserespective
(immunezonation)forenhancedliverprotectionagainstpathogenicbacteria
endothelialcellsthroughaMyd88-,establishinga
chemokinegradientthatdirectsKCstoperiportalareasoftheliverlobule,,centralvein;LSEC,
liversinusoidalendothelialcell;PAMP,pathogenassociatedmolecularpattern;PT,portaltriad;TLR,tolllikereceptor.
governingthisasymmetricalweaningandthatitwasdisruptedinduringanyoneparticularstageof
distributionandthepotentialgermfree(GF)andMyd88-deficientKCdevelopmentbutisratherthe
physiologicalfunctionofthisKCmice,butonlypartiallydisruptedinresultofadynamicprocessthat
arrangementhave,untilnow,eludedTLR4-deficientmice,suggestingdependsonthesensingofmicrobial
,co-
mechanisticinsightintothisKCSPFmiceortreatingGFmicewiththatwhilethemajorityofKCsare
,asignificant
,thesefindingsproportionaremadeupofbone
zonation,6thestudyrevealsthatthisconvincinglyestablishedthatmarrowderivedmonocytesthatare
distributionwasestablishedduringimmunezonationisnotimprintedrecruitedtotheliverinsteadystate
2
,theauthorsproposethatbutinsteadstrategicallylocatedina
thereforepossiblethatadynamicLSECssensemicrobialproductsviapatternselectedbyevolutionto
mechanismisimportanttopositionMyd88-dependentpathways,
newlyrecruitedmonocyte-derivedresponseproduceglycocalyxzonation,thecompartmentalization
Interestingly,
LSECs,butnotinKCsorsequesteringofchemokinesanothercomplementarysolutionto
hepatocytes,resultedintheproducedbyLSECsandthekeepmacrophagesinstrategic
disruptionofperiportalKCformationofachemokinegradientlocationstomaximizeimmune
zonation,,forexample,
signalinginLSECsistheprimaryperiportalzonationofKCstherestrictedlocationofLCMsin
(Figure1).Thesefindingsarethehepaticcapsuleseemsoptimized
iswellunderstoodthatLSECsareconsistentwithotherstudiestoreducethedisseminationof
exposedtorelativelyhighsupportingthekeyroleoftheperitonealbacteriaenteringtheliver
concentrationsofgut-
PAMPsinportalbloodundersteadychemokinespromotingcellinjectionofListeriaand
invitrostudieshavehintedthatTLRprocesshasbeenreportedresultedina10-foldincreaseofthe
signalinginLSECscanpromotethepreviously,theroleofMyd88liverbacterialloadsincomparison
,
adhesionmolecules;9however,byendothelialcellshighlightedbywhileKCswerepresent,theywere
.
thefirstinvivoevidencethatsensingmechanism,thatiscertainlyworthTheprimarylimitationofthis
throughMyd88signalingplaysanquestionsremainingtobeaddressedtoaddresswhethertheincreasein
importantroleinregulatingtherelatestothemechanismspromotingbacterialuptakewasduetothe
-derivedordifferencesinthefunctionof
,theperiportalversuspericentralKupffer
findingsrevealthatseveralLSEC-
derivedchemokinessuchasCXCL9circulateinthehepaticsinusoids,andobservednodifferencesintheir
andCCL17wereenrichedinthetheseproductsmightbegraduallyabilitytocapturebacteriainvitro
periportalregionsandwereclearedwhentheyreachwhencomparedwithKCsisolated
expressedatlowerlevelsinthecentrilobularregions,itwouldthusfromtheliversoflittermate
centrilobularregions,
agradientofthesechemokinesalongisaPAMPgradientinportalbloodtodesignaninsilicoapproachwith
theliversinusoids(Figure1).
Surprisingly,Myd88didnotregulateFinally,
alteringthetranscriptionofsignificanceofperiportalKCmathematicalmodelsuggestthatthe
chemokinegenesbutbyindirectlyzonationwithrespecttoabacterialspatialdistributionofKCsisthe
proteinsparticipatingintheexhibitingperiportalimmunebacterialuptakeinperiportalareas.
formationoftheendothelialzonationshowedanincreasedabilityHowever,itcannotberuledoutthat
model,theexpressionofgenesandtopreventitsspreadfromtheandpericentralmicroenvironments,
involvedinthecompositionandlivertothespleenandsystemicsuchasoxygenconcentration,
enrichedinLSECslocatedinemphasizethatmacrophagesarenotKCs,suchastheabilitytocapture
,anddegradebacteria;indeed,
3
MicrobiotaoptimiseKupffercellfunctionKEnglishetal.
periportalKCshavebeenreportedLCMsseemalsotodevelopduringhepatocytesthroughfenestrationsin
asbeinglargerandmorephagocyticweaningandtheirgenerationismurineliversinusoidalendothelial
–
-freemice5;however,;44:1182
possiblethatthesepropertiesarelostunlikeKCs,theirnumbersarenot1190.
,TaySS,McCaughan
followingisolationfromtheliveralteredinMyd88-deficientmiceand
GW,
:isCD8Tcellfate
remainsunansweredinthestudybyrecruitment,distributionanddeterminedbytheenvironment?J
;63:1005–1014.
,PeltanA,MaroofA,etal.
Intheirstudy,,thesenewfindingsDynamicimagingofexperimental
-induced
linksbetweenthegutmicrobiome,evidenceillustratingthecomplexityhepaticgranulomasdetectsKupffer
endothelialcellregulationofoflocaltissueimmunedefence,cell-restrictedantigenpresentation
toantigen-specificCD8