?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F8633%2F&rft.title=Evaluation+of+dengue+virus+infection+in+immune+cells+of+human+skin&rft.creator=Smith%2C+Amanda+Paige&rft.description=Dengue+virus+(DENV)+is+a+reemerging+infectious+agent+causing+an+estimated+50-100+million+cases+annually+and+is+endemic+in+more+than+100+countries.+Recently+there+has+been+an+increase+in+the+geographic+spread%2C+the+overall+number%2C+and+the+severity+of+disease+cases%2C+making+DENV+an+increasing+threat+to+public+health.+The+most+prevalent+of+the+arboviruses%2C+DENV+is+introduced+into+human+hosts+during+a+vector+mosquito's+blood+meal%3B+here%2C+virus+is+deposited+into+the+epidermal+and+dermal+layers+of+the+skin.+Therefore%2C+elucidating+the+cutaneous+immune+response+to+DENV+is+critical+to+our+understanding+of+the+immune+mechanisms+involved+in+protection+and+pathogenesis+of+DENV+and+to+the+development+of+effective+treatments+and+vaccines.+In+addition+to+resident+T-+and+B-cells%2C+the+skin+immune+system+includes+three+major+populations+of+innate+immune+cells%2C+dermal+dendritic+cells+(dDCs)%2C+dermal+macrophages+(dM%C3%98s)%2C+and+epidermal+Langerhans'+cells+(LCs).+These+immune+cells+are+potential+targets+of+DENV+infection.+The+receptor+profile+of+dDCs+and+dM%C3%98s+indicates+that+they+are+susceptible+to+DENV+infection%2C+however+evidence+of+this+is+lacking.+LCs+are+infected+following+ex+vivo+inoculation+of+human+skin+explants%2C+yet+their+role+in+DENV+pathogenesis+remains+unclear.+Upon+exposure+to+a+pathogen%2C+cutaneous+immune+cells+mature+and+migrate+to+the+cutaneous+draining+lymph+node+via+the+draining+lymphatics%3B+these+functions+are+critical+to+the+induction+of+adaptive+immune+responses+and+to+pathogen+clearance.+It+remains+unclear+how+DENV+infection+affects+the+maturation%2C+migration+and+survival+of+cutaneous+immune+cells.+Herein%2C+we+use+a+combination+of+in+vitro+studies+and+ex+vivo+inoculation+of+healthy+human+skin+explants+to+explore+the+role+of+cutaneous+immune+cells+in+DENV+infection.+We+investigated+the+degree+to+which+cutaneous+immune+cells+become+infected+with+DENV+and+measured+upregulation+of+activation+markers%2C+migration+out+of+the+skin%2C+and+the+life+span+of+infected+cells.+We+discovered+that+populations+of+cutaneous+DCs%2C+as+well+as+dM%C3%98s%2C+become+infected+with+DENV+upon+scarification+of+skin+with+virus.+In+vitro%2C+we+confirmed+that+DENV+infection+partially+inhibits+maturation+of+DCs+and+potentially+M%C3%98s.+Additionally%2C+DENV+infection+induces+DC+apoptosis+in+a+caspase-dependent+manner.+These+results+help+to+clarify+the+role+of+cutaneous+immune+cells+in+the+immunopathogenesis+of+DENV.&rft.date=2010-09-27&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F8633%2F1%2FSmithAP_ETD2010.pdf&rft.identifier=++Smith%2C+Amanda+Paige++(2010)+Evaluation+of+dengue+virus+infection+in+immune+cells+of+human+skin.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++