{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:20:52Z","timestamp":1789035652436,"version":"build-2803163510"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL105427"],"award-info":[{"award-number":["HL105427"]}],"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":["AI111914"],"award-info":[{"award-number":["AI111914"]}],"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":["AI123780"],"award-info":[{"award-number":["AI123780"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,2,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Tuberculosis (TB), caused by the bacterium\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      ), infects approximately one-fourth of the world\u2019s population. Inbred mouse models of TB do not reflect the pathological states and heterogeneity seen in human TB disease. Thus, we recently established a model of TB in diversity outbred (DO) mice, which displayed heterogeneity in inflammatory and protective responses following aerosol\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      infection. In the current study, we show that DO mice vaccinated with\n                      <jats:italic toggle=\"yes\">M. bovis<\/jats:italic>\n                      Bacille Calmette Guerin (BCG) are significantly protected upon\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      HN878 infection, and protection is associated with the induction of transcriptional pathways involved in transforming growth factor B (TGF-\u03b2) and Toll-like receptor (TLR)-10 signaling. Targeting lung innate pathways in BCG-vaccinated DO mice using adjuvants also further improved protection upon\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      infection by inducing genes associated with cellular responses to external stimuli, B-cell responses, as well as IL-17-producing CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell responses. Depletion of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells resulted in loss of vaccine-induced protection in DO BCG-vaccinated and adjuvant-treated\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      -infected mice. Together, our new results show that innate targeting of the lung by activating TLR pathways could induce protective pathways in T cells that significantly improve upon the protection induced by BCG vaccination. Additionally, the DO mouse model of vaccination and\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      infection can provide novel insights into immune pathways that are important for improving vaccine-induced protection against TB.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Bacille Calmette Guerin (BCG) vaccination in genetically diverse outbred (DO) mice provides significant protection against\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">Mtb)<\/jats:italic>\n                      challenge. This protection induced pathways associated with transforming growth factor B (TGF-\u03b2) receptor complex, genes associated with lung repair, and Toll-like receptor (TLR)-10 pathway. The enhanced protection observed in BCG-vaccinated mice correlated with improved formation of B-cell follicles and IL-17-producing CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell responses. CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell responses mediated the enhanced protection in the lungs of DO mice vaccinated with BCG + adjuvant, as depletion of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell responses reversed the enhanced protection. The DO mouse model of tuberculosis vaccination is a highly relevant model to probe mechanisms of vaccine-induced protection and provide novel insights into lung pathways that mediate protection. The study also found that genes associated with lung repair, including TGF-\u03b2 receptor complex pathways, were induced in BCG-vaccinated\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      -infected DO mouse lungs. The study suggests that the activation of lung innate pathways in BCG vaccination through the use of mucosal Amph CpG delivery, CD40L activation, and IL-10 neutralization could significantly enhance protection upon\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      challenge.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.03232-25","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T14:01:00Z","timestamp":1768917660000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Targeting the lung innate pathways during tuberculosis can improve vaccine-induced protection via Th17 responses in diversity outbred mice"],"prefix":"10.1128","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0231-6898","authenticated-orcid":false,"given":"Mushtaq","family":"Ahmed","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, The University of Chicago","place":["Chicago, USA"]},{"id":[{"id":"https:\/\/ror.org\/01yc7t268","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology, Washington University in St. Louis","place":["St. Louis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibali","family":"Das","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01yc7t268","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology, Washington University in St. Louis","place":["St. Louis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A.","family":"Rosa","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01yc7t268","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Washington University in St. Louis","place":["St. Louis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Rangel Moreno","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/022kthw22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center","place":["Rochester, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3521-1257","authenticated-orcid":true,"given":"Deepak","family":"Kaushal","sequence":"additional","affiliation":[{"name":"Southwest National Primate Research Center, Texas Biomedical Research Institute","place":["San Antonio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9572-3436","authenticated-orcid":true,"given":"Makedonka","family":"Mitreva","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01yc7t268","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Washington University in St. Louis","place":["St. Louis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9545-4982","authenticated-orcid":true,"given":"Shabaana A.","family":"Khader","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, The University of Chicago","place":["Chicago, USA"]},{"id":[{"id":"https:\/\/ror.org\/01yc7t268","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology, Washington University in St. Louis","place":["St. Louis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_6_2_2","unstructured":"WHO. 2022. 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