Mathematical Modeling of Tuberculosis Bacillary Counts and Cellular Populations in the Organs of Infected Mice 英文参考文献.docVIP

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Mathematical Modeling of Tuberculosis Bacillary Counts and Cellular Populations in the Organs of Infected Mice 英文参考文献.doc

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Mathematical Modeling of Tuberculosis Bacillary Counts and Cellular Populations in the Organs of Infected Mice 英文参考文献

MathematicalModelingofTuberculosisBacillaryCounts andCellularPopulationsintheOrgansofInfectedMice AntonioBru1,Pere-JoanCardona2,3* 1DepartamentodeMatema′tica Aplicada,FacultaddeMatema′ticas, UniversidadComplutensedeMadrid,Madrid,Spain,2UnitatdeTuberculosiExperimental,Fundacio′ InstitutperalaInvestigacio′ enCie`nciesdelaSalutGermansTriasiPujol,UniversitatAuto`nomadeBarcelona,Badalona,Spain,3CentrodeInvestigacio′nBiome′dicaen Red(CIBER)EnfermedadesRespiratorias,InstitutoCarlosIII,PalmadeMallorca,Spain Abstract Background:Mycobacteriumtuberculosisisaparticularlyaggressivemicroorganismandthehost’sdefenseisbasedonthe inductionofcellularimmunity,inwhichthecreationofagranulomatousstructurehasanimportantrole. Methodology:Wepresenthereanew2Dcellularautomatamodelbasedontheconceptofamultifunctionalprocessthat includeskeyfactorssuchasthechemokineattractionofthecells;theroleofinnateimmunitytriggeredbynaturalkillers; thepresenceofneutrophils;apoptosisandnecrosisofinfectedmacrophages;theremovalofdeadcellsbymacrophages, whichinducestheproductionoffoamymacrophages(FMs);thelifecycleofthebacilliasadeterminantfortheevolutionof infectedmacrophages;andtheimmuneresponse. Results:Theresultsobtainedaftertheinclusionoftwodegreesoftolerancetotheinflammatoryresponsetriggeredbythe infectionshowsthatthemodelcancoverawidespectrum,rangingfromhighly-tolerant(i.e.mice)topoorly-toleranthosts (i.e.mini-pigsorhumans). Conclusions: This model suggest that stopping bacillary growth at theonset of theinfection mightbe difficult and the importantroleplayedbyFMsinbacillarydrainageinpoorly-toleranthoststogetherwithapoptosisandinnatelymphocytes. Italsoshowsthepoorabilityofthecellularimmunitytocontroltheinfection,providesaclearprotectivecharactertothe granuloma,dueitsabilitytoattractasufficientnumberofcells,andexplainswhyanalreadyinfectedhostcanbeconstantly reinfected. Citation: Bru A, Cardona P-J (2010) Mathematical Modeling of Tuberculosis Bacillary Counts and Cellular Populations in the Organs of Infe