Protective Contributions against Invasive Streptococcus pneumoniae Pneumonia of Antibody and Th17-Cell Responses to Nasopharyngeal Colonisation 英文参考文献.docVIP

ProtectiveContributionsagainstInvasiveStreptococcus pneumoniaePneumoniaofAntibodyandTh17-Cell ResponsestoNasopharyngealColonisation JonathanM.Cohen1,2,SuneetaKhandavilli1,EmilieCamberlein1,CatherineHyams1,HelenE. Baxendale2,3,JeremyS.Brown1* 1Centre for Respiratory Research, Department of Medicine, University College London, London, United Kingdom, 2Infectious Diseases and Microbiology Unit, Child Health Institute, University College London, London, United Kingdom, 3Department of Immunology, Royal Free Hospital Medical School Campus, University College London,London,UnitedKingdom Abstract The nasopharyngeal commensal bacteria Streptococcus pneumoniae is also a frequent cause of serious infections. Nasopharyngeal colonisation with S. pneumoniae inhibits subsequent re-colonisation by inducing Th17-cell adaptive responses, whereas vaccination prevents invasive infections by inducing antibodies to S. pneumoniae capsular polysaccharides. In contrast, protection against invasive infection after nasopharyngeal colonisation with mutant S. pneumoniaestrainswasassociatedwithantibodyresponsestoproteinantigens.Theroleofcolonisation-inducedTh17-cell responses during subsequent invasive infections is unknown. Using mouse models, we show that previous colonisation withS.pneumoniaeprotectsagainstsubsequentlethalpneumoniamainlybypreventingbacteraemiawithamoremodest effect on local control of infection within the lung. Previous colonisation resulted in CD4-dependent increased levels of Th17-cell cytokines during subsequent infectious challenge. However, mice depleted of CD4 cells prior to challenge remainedprotectedagainstbacteraemia,whereasnoprotectionwasseeninantibodydeficientmiceandsimilarprotection couldbeachievedthroughpassivetransferofserum.Serumfromcolonisedmicebutnotantibodydeficientmicepromoted phagocytosisofS.pneumoniae,andpreviouslycolonisedmicewereabletorapidlyclearS.pneumoniaefromthebloodafter intravenousinoculation.Thus,despiteprimingforaTh17-cellresponseduringsub