Cytokine and Chemokine Responses of Lung Exposed to Surrogate Viral and Bacterial Infections

摘要

Theuseofinvitromodelsofcomplexinvivosystemshasyieldedmanyinsightsintothemolecularmechanismsthatunderlienormalandpathologicphysiology.Howeveralthoughthereducedcomplexityofthesemodelsisadvantageouswithregardtosomeresearchquestions,thesimplificationmayobscureoreliminatekeyinfluencesthatoccurinvivo.Wesoughttoexaminethispossibilitywithregardtothelung'sresponsetoinfection,whichmaybeinherenttoresidentlungcellsorrelatedtothesystemicresponsetopulmonaryinfection.WeusedtheinbredmousestrainsC57BL/6J,DBA/2J,andB6.129S2-IL6suptm1Kopf/sup,whichdifferintheirresponsetoinflammatoryandinfectiouschallenges,toassessinvivoresponsesoflungtosurrogateviralandbacterialinfectionandcomparedthesewithresponsesofculturedlungslicesandhumanA549cells.PulmonarycytokineconcentrationsweremeasuredbothafterinvivoinoculationofmiceandinvitroexposureoflungslicesandA549cellstosurrogateviralandbacterialinfections.Thedataindicatesimilaritiesanddifferencesinearlylungresponsestoinvivocomparedwithinvitroexposuretotheseinflammatorysubstances.Therefore,residentcellsinthelungappeartorespondtosomechallengesinastrain-independentmanner,whereassomestimulimayelicitrecruitmentofperipheralinflammatorycellsthatgeneratethesubsequentresponseinagenotype-relatedmanner.Theseresultsaddtothebodyofinformationpointingtohostgenotypeasacrucialfactorinmediatingtheseverityofmicrobialinfectionsanddemonstratethatsomeoftheseeffectsmaynotbeapparentinvitro.