{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:45:50Z","timestamp":1791477950301,"version":"4.3.4"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 AI139133"],"award-info":[{"award-number":["R01 AI139133"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R35 GM146795"],"award-info":[{"award-number":["R35 GM146795"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Dartmouth College Molecular Microbiology and Pathogenesis Program (NIH\/National Institute of Allergy and Infectious Diseases [NIAID]","award":["T32 AI007519"],"award-info":[{"award-number":["T32 AI007519"]}]},{"name":"Dartmouth College Immunology Training Program","award":["T32 AI007363"],"award-info":[{"award-number":["T32 AI007363"]}]},{"name":"Dartmouth College Cystic Fibrosis Training Program","award":["T32 HL134598"],"award-info":[{"award-number":["T32 HL134598"]}]},{"name":"CFRDP Training Core from the Cystic Fibrosis Foundation"},{"name":"The Attune CytPix","award":["2022-70410-38419"],"award-info":[{"award-number":["2022-70410-38419"]}]},{"name":"US Department of Agriculture, National Institute of Food and Agriculture"},{"name":"DartLab"},{"name":"the Immune Monitoring and Flow Cytometry Shared Resource at the Dartmouth Cancer Center"},{"name":"National Cancer Institute (NCI) Cancer Center","award":["5P30 CA023108-41"],"award-info":[{"award-number":["5P30 CA023108-41"]}]},{"name":"bioMT"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P20-GM113132"],"award-info":[{"award-number":["P20-GM113132"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P30-DK117469"],"award-info":[{"award-number":["P30-DK117469"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dartmouth Cancer Center through NCI Cancer Center","award":["P30 CA023108"],"award-info":[{"award-number":["P30 CA023108"]}]},{"name":"Nikon SoRa Spinning Disk Confocal Microscope was supported through NIH","award":["S10 OD032310"],"award-info":[{"award-number":["S10 OD032310"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alveolar macrophages (AMs) are key mediators of lung function and are potential targets for therapies during respiratory infections. TGF\u03b2 is an important regulator of AM differentiation and maintenance, but how TGF\u03b2 directly modulates the innate immune responses of AMs remains unclear. This shortcoming prevents effective targeting of AMs to improve lung function in health and disease. Here, we leveraged an optimized ex vivo AM model system, fetal liver\u2013derived alveolar-like macrophages (FLAMs), to dissect the role of TGF\u03b2 in AMs. Using transcriptional analysis, we first globally defined how TGF\u03b2 regulates gene expression of resting FLAMs. We found that TGF\u03b2 maintains the baseline metabolic state of AMs by driving lipid metabolism through oxidative phosphorylation and restricting inflammation. To better understand inflammatory regulation in FLAMs, we next directly tested how TGF\u03b2 alters the response to TLR2 agonists. While both TGF\u03b2 (+) and TGF\u03b2 (\u2212) FLAMs robustly responded to TLR2 agonists, we found an unexpected activation of type I interferon (IFN) responses in TGF\u03b2 (+) FLAMs and primary AMs. Surprisingly, mitochondrial antiviral signaling protein and the IFN regulator factors 3 and 7 were required for IFN production by TLR2 agonists and the IFN response was dependent on mitochondrial reactive oxygen species. Together, these data suggest that TGF\u03b2 modulates AM metabolic networks and innate immune signaling cascades to control inflammatory pathways in AMs.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag090","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:29:10Z","timestamp":1779168550000},"source":"Crossref","is-referenced-by-count":3,"title":["TGF\u03b2 primes alveolar-like macrophages to induce type I IFN following TLR2 activation"],"prefix":"10.1093","volume":"215","author":[{"given":"Sean M","family":"Thomas","sequence":"first","affiliation":[{"name":"Department of Microbiology, Genetics, and Immunology, College of Osteopathic Medicine, Michigan State University , East Lansing, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8983-177X","authenticated-orcid":false,"given":"Abigail P","family":"McGee","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Lebanon, NH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taryn E","family":"Vielma","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Genetics, and Immunology, College of Osteopathic Medicine, Michigan State University , East Lansing, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurisa M","family":"Ankley","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Genetics, and Immunology, College of Osteopathic Medicine, Michigan State University , East Lansing, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander W","family":"Rapp","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Lebanon, NH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla N","family":"Conner","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Genetics, and Immunology, College of Osteopathic Medicine, Michigan State University , East Lansing, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"LeSage","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Lebanon, NH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Tanner","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Lebanon, NH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor C","family":"Scheeres","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Genetics, and Immunology, College of Osteopathic Medicine, Michigan State University , East Lansing, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua J","family":"Obar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Lebanon, NH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3441-3113","authenticated-orcid":false,"given":"Andrew J","family":"Olive","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Genetics, and Immunology, College of Osteopathic Medicine, Michigan State University , East Lansing, MI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"2026051901290189000_vkag090-B1","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1002\/j.2040-4603.2016.tb00698.x","article-title":"Lung structure and the intrinsic challenges of gas exchange","volume":"6","author":"Hsia","year":"2016","journal-title":"Compr Physiol"},{"key":"2026051901290189000_vkag090-B2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/ni.3052","article-title":"The development and function of lung-resident macrophages and dendritic cells","volume":"16","author":"Kopf","year":"2015","journal-title":"Nat Immunol"},{"key":"2026051901290189000_vkag090-B3","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41385-019-0158-0","article-title":"Regulatory cytokine function in the respiratory tract","volume":"12","author":"Branchett","year":"2019","journal-title":"Mucosal Immunol"},{"key":"2026051901290189000_vkag090-B4","doi-asserted-by":"crossref","first-page":"617879","DOI":"10.3389\/fcell.2020.617879","article-title":"Tissue-resident macrophage development and function","volume":"8","author":"Wu","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"2026051901290189000_vkag090-B5","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.immuni.2016.02.017","article-title":"Yolk sac macrophages, fetal liver, and adult monocytes can colonize an empty niche and develop into functional tissue-resident macrophages","volume":"44","author":"van de Laar","year":"2016","journal-title":"Immunity"},{"key":"2026051901290189000_vkag090-B6","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.immuni.2017.10.007","article-title":"The cytokine TGF-\u03b2 promotes the development and homeostasis of alveolar macrophages","volume":"47","author":"Yu","year":"2017","journal-title":"Immunity"},{"key":"2026051901290189000_vkag090-B7","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/imm.13143","article-title":"Tissue-resident innate immunity in the lung","volume":"159","author":"Ardain","year":"2020","journal-title":"Immunology"},{"key":"2026051901290189000_vkag090-B8","doi-asserted-by":"crossref","first-page":"eaaw6693","DOI":"10.1126\/sciimmunol.aaw6693","article-title":"Alveolar macrophages generate a noncanonical NRF2-driven transcriptional response to Mycobacterium tuberculosis in vivo","volume":"4","author":"Rothchild","year":"2019","journal-title":"Sci Immunol"},{"key":"2026051901290189000_vkag090-B9","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.celrep.2019.12.033","article-title":"Dual RNA-seq of Mtb-infected macrophages in vivo reveals ontologically distinct host-pathogen interactions","volume":"30","author":"Pisu","year":"2020","journal-title":"Cell 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