{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T10:16:04Z","timestamp":1792232164512,"version":"4.4.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T00:00:00Z","timestamp":1554681600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A proportion of tuberculosis (TB) case contacts do not become infected, even when heavily exposed. We studied the innate immune responses of TB case contacts to understand their role in protection against infection with Mycobacterium tuberculosis, termed \u201cearly clearance.\u201d<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Indonesian household contacts of TB cases were tested for interferon-\u03b3 release assay (IGRA) conversion between baseline and 14 weeks post recruitment. Blood cell populations and ex vivo innate whole blood cytokine responses were measured at baseline and, in a subgroup, flow cytometry was performed at weeks 2 and 14. Immunological characteristics were measured for early clearers, defined as a persistently negative IGRA at 3 months, and converters, whose IGRA converted from negative to positive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 1347 case contacts, 317 were early clearers and 116 were converters. Flow cytometry showed a resolving innate cellular response from 2 to 14 weeks in persistently IGRA-negative contacts but not converters. There were no differences in cytokine responses to mycobacterial stimuli, but compared to converters, persistently IGRA-negative contacts produced more proinflammatory cytokines following heterologous stimulation with Escherichia coli and Streptococcus pneumoniae.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Early clearance of M. tuberculosis is associated with enhanced heterologous innate immune responses similar to those activated during induction of trained immunity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiz147","type":"journal-article","created":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T23:31:37Z","timestamp":1554247897000},"source":"Crossref","is-referenced-by-count":41,"title":["Early Clearance of Mycobacterium tuberculosis Is Associated With Increased Innate Immune Responses"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9672-1352","authenticated-orcid":false,"given":"Ayesha J","family":"Verrall","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bachti","family":"Alisjahbana","sequence":"additional","affiliation":[{"name":"TB-HIV Research Center, Faculty of Medicine, Universitas Padjadjaran, Nijmegen, The Netherlands"},{"name":"Department of Internal Medicine, Faculty of Medicine, Universitas Padajdaran, Hasan Sadikin Hospital, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lika","family":"Apriani","sequence":"additional","affiliation":[{"name":"TB-HIV Research Center, Faculty of Medicine, Universitas Padjadjaran, Nijmegen, The Netherlands"},{"name":"Department of Public Health, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjan","family":"van Laarhoven","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie A C M","family":"Koeken","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suszanne","family":"van Dorp","sequence":"additional","affiliation":[{"name":"Department 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