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Chronic HIV Infection Enhances the Responsiveness of Antigen Presenting Cells to Commensal Lactobacillus.doc

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Chronic HIV Infection Enhances the Responsiveness of Antigen Presenting Cells to Commensal Lactobacillus

ChronicHIVInfectionEnhancestheResponsivenessof AntigenPresentingCellstoCommensalLactobacillus LaurenH.Nagy1,IrinaGrishina1,MonicaMacal1,LaurenA.Hirao1,WilliamK.Hu1,SumathiSankaran- Walters1,ChristopherA.Gaulke1,RichardPollard1,JenniferBrown2,MariaSuni4,AndreasJ.Baumler1, SmitaGhanekar4,MariaL.Marco3,SatyaDandekar1* 1DepartmentofMedicalMicrobiologyandImmunology,UniversityofCaliforniaDavis,Davis,California,UnitedStatesofAmerica, 2DepartmentofInternalMedicine, UniversityofCaliforniaDavis,Davis,California,UnitedStatesofAmerica,3FoodScienceandTechnologyUniversityofCaliforniaDavis,Davis,California,USA,4Becton DickinsonBiosciences,SanJose,California,UnitedStatesofAmerica Abstract Chronicimmuneactivationdespitelong-termtherapyposesanobstacletoimmunerecoveryinHIVinfection.Theroleof antigenpresentingcells(APCs)inchronicimmuneactivationduringHIVinfectionremainstobefullydetermined.APCs,the frontline of immune defense against pathogens, are capable of distinguishing between pathogens and non-pathogenic, commensalbacteria.WehypothesizedthatHIVinfectioninducesdysfunctioninAPCimmunerecognitionandresponseto some commensal bacteria and that this may promote chronic immune activation. Therefore we examined APC inflammatorycytokineresponsestocommensallactobacilli.WefoundthatAPCsfromHIV-infectedpatientsproducedan enhanced inflammatory response to Lactobacillus plantarum WCFS1 as compared to APCs from healthy, HIV-negative controls. Increased APC expression of TLR2 and CD36, signaling through p38-MAPK, and decreased expression of MAP kinasephosphatase-1(MKP-1)inHIVinfectionwasassociatedwiththisheightenedimmuneresponse.Ourfindingssuggest thatchronicHIVinfectionenhancestheresponsivenessofAPCstocommensallactobacilli,amechanismthatmaypartly contributetochronicimmuneactivation. Citation: Nagy LH, Grishina I, Macal M, Hirao LA, Hu WK, et al. (2013) Chronic HIV Infection Enhances the Responsiveness of Antigen Presenting Cells to CommensalLactobacillus.PLoSONE8(8):e72789.doi:10.1371/