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These agents enhance the numbers and function of regulatory T cells (Tregs), which are important in controlling inflammatory diseases. However, elevated Treg levels increase susceptibility to infections, including histoplasmosis. We determined the mechanism by which Tregs expand in TNF-neutralized mice infected with<jats:named-content content-type=\"genus-species\">Histoplasma capsulatum<\/jats:named-content>. Lung CD11c<jats:sup>+<\/jats:sup>CD11b<jats:sup>+<\/jats:sup>dendritic cells (DCs), but not alveolar macrophages, from<jats:named-content content-type=\"genus-species\">H. capsulatum<\/jats:named-content>-infected mice treated with anti-TNF induced a higher percentage of Tregs than control DCs<jats:italic>in vitro<\/jats:italic>. CD11b<jats:sup>+<\/jats:sup>CD103<jats:sup>+<\/jats:sup>DCs, understood to be unique to the intestines, were augmented in lungs with anti-TNF treatment. In the absence of this subset, DCs from anti-TNF-treated mice failed to amplify Tregs<jats:italic>in vitro<\/jats:italic>. CD11b<jats:sup>+<\/jats:sup>CD103<jats:sup>+<\/jats:sup>DCs from TNF-neutralized mice displayed higher retinaldehyde dehydrogenase 2 (RALDH2) gene expression, and CD11b<jats:sup>+<\/jats:sup>CD103<jats:sup>+<\/jats:sup>RALDH<jats:sup>+<\/jats:sup>DCs exhibited greater enzyme activity. To determine if CD11b<jats:sup>+<\/jats:sup>CD103<jats:sup>+<\/jats:sup>DCs migrated from gut to lung, fluorescent beads were delivered to the gut via oral gavage, and the lungs were assessed for bead-containing DCs. Anti-TNF induced migration of CD11b<jats:sup>+<\/jats:sup>CD103<jats:sup>+<\/jats:sup>DCs from the gut to the lung that enhanced the generation of Tregs in<jats:named-content content-type=\"genus-species\">H. capsulatum<\/jats:named-content>-infected mice. Therefore, TNF neutralization promotes susceptibility to pulmonary<jats:named-content content-type=\"genus-species\">H. capsulatum<\/jats:named-content>infection by promoting a gut\/lung migration of DCs that enhances Tregs.<\/jats:p>","DOI":"10.1128\/iai.00109-18","type":"journal-article","created":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T10:12:21Z","timestamp":1522145541000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["Tumor Necrosis Factor Alpha Antagonism Reveals a Gut\/Lung Axis That Amplifies Regulatory T Cells in a Pulmonary Fungal Infection"],"prefix":"10.1128","volume":"86","author":[{"given":"Jamie L.","family":"Tweedle","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA"},{"name":"Program of Pathobiology and Molecular Medicine, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"George S.","family":"Deepe","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA"},{"name":"Veterans Affairs Hospital, Cincinnati, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(11)60839-2"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200206-563OC"},{"key":"e_1_3_3_4_2","doi-asserted-by":"crossref","first-page":"6072","DOI":"10.4049\/jimmunol.160.12.6072","article-title":"Blockade of endogenous TNF-alpha exacerbates primary and secondary pulmonary histoplasmosis by differential mechanisms","volume":"160","author":"Allendoerfer R","year":"1998","unstructured":"Allendoerfer R, Deepe GS. 1998. 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