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This could be explained by an IFN-\u03b3-independent adaptive immune response, or an effective innate host response clearing\n                    <jats:italic>Mycobacterium tuberculosis (Mtb)<\/jats:italic>\n                    without adaptive immunity. In heavily exposed Indonesian tuberculosis household contacts (n\u2009=\u20091347), a persistently IGRA negative status was associated with presence of a BCG scar, and - especially among those with a BCG scar - with altered innate immune cells dynamics, higher heterologous (\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    -induced) proinflammatory cytokine production, and higher inflammatory proteins in the IGRA mitogen tube. Neither circulating concentrations of\n                    <jats:italic>Mtb<\/jats:italic>\n                    -specific antibodies nor functional antibody activity associated with IGRA status at baseline or follow-up. In a cohort of adults in a low tuberculosis incidence setting, BCG vaccination induced heterologous innate cytokine production, but only marginally affected\n                    <jats:italic>Mtb-<\/jats:italic>\n                    specific antibody profiles. Our findings suggest that a more efficient host innate immune response, rather than a humoral response, mediates early clearance of\n                    <jats:italic>Mtb<\/jats:italic>\n                    . The protective effect of BCG vaccination against\n                    <jats:italic>Mtb<\/jats:italic>\n                    infection may be linked to innate immune priming, also termed \u2018trained immunity\u2019.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-55501-6","type":"journal-article","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T21:09:36Z","timestamp":1735852176000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3252-1201","authenticated-orcid":false,"given":"Todia P.","family":"Setiabudiawan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lika","family":"Apriani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayesha J.","family":"Verrall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fitria","family":"Utami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes R.","family":"Indrati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline P.","family":"Halim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Kaplonek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadar","family":"Malca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica Shih-Lu","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone J. 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The research included Indonesian researchers throughout the research process, as their participation was essential for the design and implementation of the study. Capacity-building plans for Indonesian researchers were discussed and have been implemented, with T.P.S. and L.A. exemplifying the success of these efforts within our longstanding collaboration. Roles and responsibilities were agreed among collaborators ahead of the research. This work includes findings that are locally relevant which have been determined in collaboration with local partners. This research was not severely restricted or prohibited in the setting of the researchers and does not result in stigmatization, incrimination, discrimination or personal risk to participants. The study has been approved by a local ethics review committee. Local and regional research relevant to our study was taken into account in citations. This research does not involve health, safety, security or other risk to researchers. Benefit-sharing measures have been discussed among all collaborators regarding biological materials transferred out of Indonesia.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Inclusion & ethics"}}],"article-number":"309"}}