{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T19:45:15Z","timestamp":1774467915115,"version":"3.50.1"},"reference-count":34,"publisher":"Hindawi Limited","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p>The contribution of interleukin- (IL-) 4 receptor-alpha- (R<jats:italic>\u03b1<\/jats:italic>-) dependent events in the pathogenesis of tuberculosis (TB) is controversial. We have recently shown IL-13 overexpression in mice to cause recrudescent<jats:italic>Mtb<\/jats:italic>replication and centrally necrotizing granulomas strongly resembling pathology of human TB. A deletion of IL-4R<jats:italic>\u03b1<\/jats:italic>completely abrogates TB tissue pathology in these mice. To validate our results in human TB patients, we here determined the association of distinct variants of the<jats:italic>IL4<\/jats:italic>,<jats:italic>IL13<\/jats:italic>,<jats:italic>IL4RA<\/jats:italic>,<jats:italic>IL13RA1<\/jats:italic>, and<jats:italic>IL13RA2<\/jats:italic>genes with cavity formation in a large Ghanaian cohort of HIV-negative individuals with newly diagnosed pulmonary TB. In fact, the structural variant of the<jats:italic>IL4RA<\/jats:italic>I50V, previously shown to result in enhanced signal transduction, was significantly associated with greater cavity size, and a variant of<jats:italic>IL13RA2<\/jats:italic>was associated with disease in females. To evaluate whether the human-like TB pathology in IL-13-overexpressing mice is specifically mediated through the IL-4R<jats:italic>\u03b1<\/jats:italic>subunit, we analyzed IL-13 transgenic mice with a genetic ablation of the IL-4R<jats:italic>\u03b1<\/jats:italic>. In these mice, the IL-13-mediated increased susceptibility, human-like pathology of collagen deposition around centrally necrotizing granulomas, and alternative macrophage activation were abolished. Together, our genetic association study in human TB patients further supports the assumption that IL-13\/IL-4R<jats:italic>\u03b1<\/jats:italic>-dependent mechanisms are involved in mediating tissue pathology of human TB.<\/jats:p>","DOI":"10.1155\/2016\/4245028","type":"journal-article","created":{"date-parts":[[2016,2,10]],"date-time":"2016-02-10T21:04:52Z","timestamp":1455138292000},"page":"1-9","source":"Crossref","is-referenced-by-count":14,"title":["A Mutation in<i>IL4RA<\/i>Is Associated with the Degree of Pathology in Human TB Patients"],"prefix":"10.1155","volume":"2016","author":[{"given":"Christoph","family":"H\u00f6lscher","sequence":"first","affiliation":[{"name":"Infection Immunology, Research Center Borstel, Parkallee 22, 23845 Borstel, Germany"},{"name":"German Center for Infection Research, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Heitmann","sequence":"additional","affiliation":[{"name":"Infection Immunology, Research 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