{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:47:50Z","timestamp":1790473670182,"version":"4.1.0"},"reference-count":23,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Harry L. Willett Foundation, Denver, CO."}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Mycobacterium avium<\/jats:italic>\n                      complex, is the most common nontuberculous mycobacterial respiratory pathogen in humans. Disease mechanisms are poorly understood due to the absence of a reliable animal model for\n                      <jats:italic>M<\/jats:italic>\n                      .\n                      <jats:italic>avium<\/jats:italic>\n                      complex pulmonary disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      The objectives of this study were to\n                      <jats:bold>a<\/jats:bold>\n                      ssess the susceptibility, immunologic and histopathologic responses of the common marmoset (\n                      <jats:italic>Callithrix jacchus<\/jats:italic>\n                      ) to\n                      <jats:italic>M<\/jats:italic>\n                      .\n                      <jats:italic>avium<\/jats:italic>\n                      complex pulmonary infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      7 adult female marmosets underwent endobronchial inoculation with 10\n                      <jats:sup>8<\/jats:sup>\n                      colony-forming units\n                      <jats:italic>of M<\/jats:italic>\n                      .\n                      <jats:italic>intracellulare<\/jats:italic>\n                      and were monitored for 30 or 60 days. Chest radiograph was assessed at baseline (prior to infection) and at the time of sacrifice (30 days for 3 animals and 60 days for 4 animals), and bronchoalveolar lavage cytokines, histopathology and cultures of the bronchoalveolar lavage, lungs, liver and kidney were assessed at time of sacrifice. Serum cytokines were monitored at baseline and weekly for 30 days for all animals and at 60 days for those alive. Group differences in serum cytokine measurements between those that tested positive versus negative for the\n                      <jats:italic>M<\/jats:italic>\n                      .\n                      <jats:italic>intracellulare<\/jats:italic>\n                      infection were assessed using a series of linear mixed models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Measurements and main results<\/jats:title>\n                    <jats:p>\n                      Five of seven animals (two at 30 days and three at 60 days of infection) had positive lung cultures for\n                      <jats:italic>M<\/jats:italic>\n                      .\n                      <jats:italic>intracellulare<\/jats:italic>\n                      . Extra-pulmonary cultures were positive in three animals. All animals appeared healthy throughout the study. All five animals with positive lung cultures had radiographic changes consistent with pneumonitis. At 30 days, those with\n                      <jats:italic>M<\/jats:italic>\n                      .\n                      <jats:italic>intracellulare<\/jats:italic>\n                      lung infection showed granulomatous inflammation, while at 60 days there were fewer inflammatory changes but bronchiectasis was noted. The cytokine response in the bronchoalveolar lavage fluid was uniformly greater in the animals with positive\n                      <jats:italic>M<\/jats:italic>\n                      .\n                      <jats:italic>intracellulare<\/jats:italic>\n                      cultures than those without a productive infection, with greater levels at 30-days compared to 60-days. Similarly, serum cytokines were more elevated in the animals that had positive\n                      <jats:italic>M<\/jats:italic>\n                      .\n                      <jats:italic>intracellulare<\/jats:italic>\n                      cultures compared to those without a productive infection, peaking 14\u201321 days after inoculation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Endobronchial instillation of\n                      <jats:italic>M<\/jats:italic>\n                      .\n                      <jats:italic>intracellulare<\/jats:italic>\n                      resulted in pulmonary mycobacterial infection in marmosets with a differential immune response, radiographic and histopathologic abnormalities, and an indolent course consistent with\n                      <jats:italic>M<\/jats:italic>\n                      .\n                      <jats:italic>avium<\/jats:italic>\n                      complex lung infection in humans.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0260563","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T13:38:52Z","timestamp":1678369132000},"page":"e0260563","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["A marmoset model for Mycobacterium avium complex pulmonary disease"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5230-1062","authenticated-orcid":true,"given":"Jay","family":"Peters","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego Jose","family":"Maselli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandeep","family":"Mangat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline J.","family":"Coalson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Hinojosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Giavedoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A.","family":"Brown-Elliott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Griffith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"pone.0260563.ref001","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/978-3-319-93473-0_7","volume-title":"Nontuberculous Mycobacterial Disease: a comprehensive approach to diagnosis and management","author":"S Daniel-Wayman","year":"2019","edition":"1"},{"key":"pone.0260563.ref002","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/978-3-319-93473-0_8","volume-title":"Nontuberculous Mycobacterial Disease: a comprehensive approach to diagnosis and management","author":"D Wagner","year":"2019","edition":"1"},{"key":"pone.0260563.ref003","first-page":"310","volume-title":"Nontuberculous Mycobacterial Disease: a comprehensive approach to diagnosis and management,","author":"MR Holt","year":"2019","edition":"1"},{"issue":"1","key":"pone.0260563.ref004","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.00250-2019","article-title":"Non-tuberculous mycobacterial pulmonary disease","volume":"54","author":"S Cowman","year":"2019","journal-title":"Eur Respir J"},{"issue":"3","key":"pone.0260563.ref005","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1055\/s-0038-1660472","article-title":"Treatment of Mycobacterium avium Complex (MAC).","volume":"39","author":"DE Griffith","year":"2018","journal-title":"Semin Respir Crit Care Med"},{"issue":"6","key":"pone.0260563.ref006","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1378\/chest.12-0494","article-title":"Clinical significance of the differentiation between Mycobacterium avium and Mycobacterium intracellulare in M","volume":"142","author":"WJ Koh","year":"2012","journal-title":"avium complex lung disease. Chest"},{"issue":"2","key":"pone.0260563.ref007","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.diagmicrobio.2017.02.017","article-title":"Distribution and clinical significance of Mycobacterium avium complex species isolated from respiratory specimens","volume":"88","author":"SY Kim","year":"2017","journal-title":"Diagn Microbiol Infect Dis"},{"key":"pone.0260563.ref008","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/978-3-319-93473-0_4","volume-title":"Nontuberculous Mycobacterial Disease: a comprehensive approach to diagnosis and management","author":"E. 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Weatherall","year":"2006","journal-title":"The use of non-human primates in research"},{"key":"pone.0260563.ref016","volume-title":"Guide for the Care and Use of Laboratory Animals of the National Institutes of Health (NIH), the Office of Animal Welfare","year":"2011","edition":"8"},{"key":"pone.0260563.ref017","first-page":"2018","volume-title":"20: CLSI M24, Susceptibility Testing of Mycobacteria, Nocardia spp, and Other Aerobic Actinomycetes.","edition":"3"},{"key":"pone.0260563.ref018","volume-title":"Laboratory Detection and Identification of Mycobacteria","author":"CLSI M48","year":"2018","edition":"2"},{"issue":"6","key":"pone.0260563.ref019","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1164\/rccm.201503-0444OC","article-title":"Semiquantitative Culture Analysis during Therapy for Mycobacterium avium Complex Lung Disease","volume":"192","author":"DE Griffith","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"issue":"8","key":"pone.0260563.ref020","doi-asserted-by":"crossref","first-page":"3482","DOI":"10.1128\/iai.61.8.3482-3489.1993","article-title":"Cytokine production at the site of disease in human tuberculosis","volume":"61","author":"PF Barnes","year":"1993","journal-title":"Infect Immun"},{"issue":"32","key":"pone.0260563.ref021","first-page":"E2997","article-title":"Macrophage migration inhibitory factor (MIF) is a critical mediator of the innate immune response to Mycobacterium tuberculosis.","volume":"110","author":"R Das","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"pone.0260563.ref022","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1358\/dnp.2010.23.4.1453629","article-title":"Macrophage migration inhibitory factor (MIF): a promising biomarker.","volume":"23","author":"Gerrit Grieb","year":"2010","journal-title":"Drug News Perspect"},{"issue":"2","key":"pone.0260563.ref023","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.ccm.2012.02.002","article-title":"Bronchiectasis and nontuberculous mycobacterial disease.","volume":"33","author":"DE Griffith","year":"2012","journal-title":"Clin Chest Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0260563","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T13:39:19Z","timestamp":1678369159000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0260563"}},"subtitle":[],"editor":[{"given":"Selvakumar","family":"Subbian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,3,9]]},"references-count":23,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0260563","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.11.15.468600","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,9]]}}}