{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:40:00Z","timestamp":1793040000385,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014713","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T00:00:00Z","timestamp":1792972800000}}],"reference-count":88,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI066302"],"award-info":[{"award-number":["AI066302"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI075039"],"award-info":[{"award-number":["AI075039"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI155634"],"award-info":[{"award-number":["AI155634"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sidney Mac Donald Russell Family fellowship from the UC Berkeley Center for Emerging and Neglected Diseases","id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (Mtb) is a robust activator of innate immunity. While innate immune activation of macrophages can impact Mtb replication\n                    <jats:italic>in vitro<\/jats:italic>\n                    , there is little\n                    <jats:italic>in vivo<\/jats:italic>\n                    evidence that the innate immune system controls Mtb before the onset of adaptive immunity. Prior work has generally used specific pathogen-free (SPF) mouse models and relatively large infectious doses, which may obscure the capacity of innate immunity to control Mtb. Here, we performed ultra-low dose Mtb infections and found that the initial innate immune response was unable to curb even minimal Mtb infectious doses. Additionally, we primed the immune systems of C57BL\/6 mice by co-housing with \u201cpet shop\u201d mice prior to Mtb exposure. Co-housed mice were as susceptible to Mtb infection as SPF mice. To pre-activate innate immunity at the site of Mtb infection more specifically, we also infected the lungs of mice with\n                    <jats:italic>Legionella pneumophila<\/jats:italic>\n                    (Lp) prior to Mtb. Innate immunity alone can clear large doses (&gt;100,000 CFU) of Lp from the lung within a few days. However, priming the mouse lung by pre-infection with Lp only modestly reduced Mtb CFU compared to mice infected with only Mtb, indicating that Mtb can robustly replicate even in the presence of a strong anti-bacterial innate response. We performed single-cell RNA-sequencing on myeloid cells from mice either infected with Mtb alone or mice primed with Lp. We found that Lp priming before Mtb infection induced measurable changes in myeloid cells responding to Mtb, but these changes had little effect on innate control of Mtb. Together, these data demonstrate the robust resistance of Mtb to innate immune clearance under diverse experimental conditions.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014713","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:50:10Z","timestamp":1792605010000},"page":"e1014713","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diverse infection models demonstrate robust resistance of Mycobacterium tuberculosis to innate immunity"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6911-3391","authenticated-orcid":true,"given":"Marian R.","family":"Fairgrieve","sequence":"first","affiliation":[{"name":"University of California","place":["Berkeley, California, United States of America"],"department":["Department of Molecular and Cell Biology, Division of Immunology and Molecular Medicine"]},{"name":"Howard Hughes Medical Institute, University of California","place":["Berkeley, California, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella C.","family":"Brydon","sequence":"additional","affiliation":[{"name":"University of California","place":["Berkeley, California, United States of America"],"department":["Department of Molecular and Cell Biology, Division of Immunology and Molecular Medicine"]},{"name":"Howard Hughes Medical Institute, University of California","place":["Berkeley, California, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto A.","family":"Chavez","sequence":"additional","affiliation":[{"name":"University of California","place":["Berkeley, California, United States of America"],"department":["Department of Molecular and Cell Biology, Division of Immunology and Molecular Medicine"]},{"name":"Howard Hughes Medical Institute, University of California","place":["Berkeley, California, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7843-1503","authenticated-orcid":true,"given":"Dmitri I.","family":"Kotov","sequence":"additional","affiliation":[{"name":"University of California","place":["Berkeley, California, United States of America"],"department":["Department of Molecular and Cell Biology, Division of Immunology and Molecular Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6686-3912","authenticated-orcid":true,"given":"Russell E.","family":"Vance","sequence":"additional","affiliation":[{"name":"University of California","place":["Berkeley, California, United States of America"],"department":["Department of Molecular and Cell Biology, Division of Immunology and Molecular Medicine"]},{"name":"Howard Hughes Medical Institute, University of California","place":["Berkeley, California, United States of America"]},{"name":"Cancer Research Laboratory, University of California","place":["Berkeley, California, United States of America"]},{"name":"Center for Emerging and Neglected Diseases, University of California","place":["Berkeley, California, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"ppat.1014713.ref001","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1146\/annurev-immunol-093019-010426","article-title":"The Innate Immune Response to Mycobacterium tuberculosis Infection","volume":"39","author":"MM Ravesloot-Ch\u00e1vez","year":"2021","journal-title":"Annu Rev Immunol"},{"issue":"3","key":"ppat.1014713.ref002","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.chom.2018.08.001","article-title":"Alveolar Macrophages Provide an Early Mycobacterium tuberculosis Niche and Initiate Dissemination","volume":"24","author":"SB Cohen","year":"2018","journal-title":"Cell Host 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