Experimental human challenge defines distinct pneumococcal kinetic profiles and mucosal responses between colonized and non-colonized adults

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dc.contributorLab. Bacteriologiapt_BR
dc.contributor.authorNikolaou, Elissavetpt_BR
dc.contributor.authorJochems, Simon P.pt_BR
dc.contributor.authorMitsi, Elenapt_BR
dc.contributor.authorPojar, Sherinpt_BR
dc.contributor.authorBlizard, Anniept_BR
dc.contributor.authorReiné, Jesuspt_BR
dc.contributor.authorSolórzano, Carlapt_BR
dc.contributor.authorNegera, Edessapt_BR
dc.contributor.authorCarniel, Beatrizpt_BR
dc.contributor.authorSchanoski, Alessandra Soarespt_BR
dc.contributor.authorConnor, Victoriapt_BR
dc.contributor.authorAdler, Hughpt_BR
dc.contributor.authorZaidi, Seher R.pt_BR
dc.contributor.authorHales, Cazpt_BR
dc.contributor.authorHill, Helenpt_BR
dc.contributor.authorHyder-Wright, Angiept_BR
dc.contributor.authorGordon, Stephen B.pt_BR
dc.contributor.authorRylance, Jamiept_BR
dc.contributor.authorFerreira, Daniela M.pt_BR
dc.date.accessioned2021-01-15T18:30:54Z-
dc.date.available2021-01-15T18:30:54Z-
dc.date.issued2021pt_BR
dc.identifier.citationNikolaou E, Jochems SP., Mitsi E, Pojar S, Blizard A, Reiné J, et al. Experimental human challenge defines distinct pneumococcal kinetic profiles and mucosal responses between colonized and non-colonized adults. mBio. 2021 Jan;12(1):e02020-20. doi:10.1128/mBio.02020-20.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/3447-
dc.description.abstractColonization of the upper respiratory tract with Streptococcus pneumoniae is the precursor of pneumococcal pneumonia and invasive disease. Following exposure, however, it is unclear which human immune mechanisms determine whether a pathogen will colonize. We used a human challenge model to investigate host-pathogen interactions in the first hours and days following intranasal exposure to Streptococcus pneumoniae. Using a novel home sampling method, we measured early immune responses and bacterial density dynamics in the nose and saliva after volunteers were experimentally exposed to pneumococcus. Here, we show that nasal colonization can take up to 24 h to become established. Also, the following two distinct bacterial clearance profiles were associated with protection: nasal clearers with immediate clearance of bacteria in the nose by the activity of pre-existent mucosal neutrophils and saliva clearers with detectable pneumococcus in saliva at 1 h post challenge and delayed clearance mediated by an inflammatory response and increased neutrophil activity 24 h post bacterial encounter. This study describes, for the first time, how colonization with a bacterium is established in humans, signifying that the correlates of protection against pneumococcal colonization, which can be used to inform design and testing of novel vaccine candidates, could be valid for subsets of protected individuals. IMPORTANCE: Occurrence of lower respiratory tract infections requires prior colonization of the upper respiratory tract with a pathogen. Most bacterial infection and colonization studies have been performed in murine and in vitro models due to the current invasive sampling methodology of the upper respiratory tract, both of which poorly reflect the complexity of host-pathogen interactions in the human nose. Self-collecting saliva and nasal lining fluid at home is a fast, low-cost, noninvasive, high-frequency sampling platform for continuous monitoring of bacterial encounter at defined time points relative to exposure. Our study demonstrates for the first time that, in humans, there are distinct profiles of pneumococcal colonization kinetics, distinguished by speed of appearance in saliva, local phagocytic function, and acute mucosal inflammatory responses, which may either recruit or activate neutrophils. These data are important for the design and testing of novel vaccine candidates.pt_BR
dc.description.sponsorshipConselho de Pesquisa Médicapt_BR
dc.description.sponsorshipBill & Melinda Gates Foundationpt_BR
dc.description.sponsorshipWellcome Trustpt_BR
dc.format.extente02020-20pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofmBiopt_BR
dc.rightsOpen Accesspt_BR
dc.titleExperimental human challenge defines distinct pneumococcal kinetic profiles and mucosal responses between colonized and non-colonized adultspt_BR
dc.typeArticlept_BR
dc.identifier.doi10.1128/mBio.02020-20pt_BR
dc.identifier.urlhttps://doi.org/10.1128/mBio.02020-20pt_BR
dc.contributor.externalLiverpool School of Tropical Medicine (LSTM)pt_BR
dc.contributor.externalLeiden University Medical Center (LUMC)pt_BR
dc.contributor.externalRoyal Liverpool and Broadgreen University Hospitals NHS Trustpt_BR
dc.contributor.externalCarnegie Mellon Universitypt_BR
dc.identifier.citationvolume12pt_BR
dc.identifier.citationissue1pt_BR
dc.subject.keywordStreptococcus pneumoniaept_BR
dc.subject.keywordcolonizationpt_BR
dc.subject.keywordsalivapt_BR
dc.subject.keywordnasal lining fluidpt_BR
dc.subject.keywordneutrophil acquisitionpt_BR
dc.subject.keywordcytokinespt_BR
dc.subject.keywordcontrolled human infectionpt_BR
dc.subject.keywordhost-pathogens interactionspt_BR
dc.relation.ispartofabbreviatedmBiopt_BR
dc.identifier.citationabntv. 14, n. 1, e02020-20, jan. 2021pt_BR
dc.identifier.citationvancouver2021 Jan;12(1):e02020-20pt_BR
dc.contributor.butantanSoares Schanoski, Alessandra|:Pesquisador|:Lab. Bacteriologiapt_BR
dc.sponsorship.butantanConselho de Pesquisa Médica¦¦MR/M011569/1pt_BR
dc.sponsorship.butantanBill & Melinda Gates Foundation¦¦OPP1117728pt_BR
dc.sponsorship.butantanWellcome Trust¦¦104936/Z/14/Zpt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
item.grantfulltextembargo_29990101-
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