{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:31:06Z","timestamp":1792690266538,"version":"4.5.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Tuberculosis (TB) is a major health problem characterized by an immuno-endocrine imbalance: elevated plasma levels of cortisol and pro- and anti-inflammatory mediators, as well as reduced levels of dehydroepiandrosterone. The etiological agent, Mycobacterium tuberculosis (Mtb), is captured by pulmonary macrophages (Mf), whose activation is necessary to cope with the control of Mtb, however, excessive activation of the inflammatory response also leads to tissue damage. Glucocorticoids (GC) are critical elements to counteract the immunoinflammatory reaction, and peroxisome proliferator-activated receptors (PPARs) are also involved in this regard. The primary forms of these receptors are PPAR\u03d2, PPAR\u03b1, and PPAR\u03b2\/\u03b4, the former being the most involved in anti-inflammatory responses. In this work, we seek to gain some insight into the contribution of PPAR\u03d2 in immuno-endocrine-metabolic interactions by focusing on clinical studies in pulmonary TB patients and in vitro experiments on a Mf cell line.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We found that TB patients, at the time of diagnosis, showed increased expression of the PPAR\u03d2 transcript in their peripheral blood mononuclear cells, positively associated with circulating cortisol and related to disease severity. Given this background, we investigated the expression of PPAR\u03d2 (RT-qPCR) in radiation-killed Mtb-stimulated human Mf. The Mtb stimulation of Mf derived from the human line THP1 significantly increased the expression of PPAR\u03d2, while the activation of this receptor by a specific agonist decreased the expression of pro- and anti-inflammatory cytokines (IL-1\u03b2 and IL-10). As expected, the addition of GC to stimulated cultures reduced IL-1\u03b2 production, while cortisol treatment together with the PPAR\u03d2 agonist lowered the levels of this proinflammatory cytokine in stimulated cultures. The addition of RU486, a glucocorticoid receptor antagonist, only reversed the inhibition produced by the addition of GC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The current results provide a stimulating background for further analysis of the interconnection between PPARs and steroid hormones in the context of Mtb infection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2023.1067464","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T15:06:08Z","timestamp":1682694368000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Studies on the contribution of PPAR Gamma to tuberculosis physiopathology"],"prefix":"10.3389","volume":"13","author":[{"given":"Ariana","family":"D\u00edaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"D\u2019Attilio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Penas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Bongiovanni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefan\u00eda","family":"Massa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Cevey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Santucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Bottasso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Goren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Luisa","family":"Bay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/383829","article-title":"PPARgamma expression and function in mycobacterial infection: roles in lipid metabolism, immunity, and bacterial killing","volume":"2012","author":"Almeida","year":"2012","journal-title":"PPAR Res."},{"key":"B2","article-title":"The paradigm shift 2018-2022","volume-title":"Global plan to end TB: 2018-2022","year":"2019"},{"key":"B3","unstructured":"Global tuberculosis report 2022"},{"key":"B4","unstructured":"Global tuberculosis report 2021"},{"key":"B5","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.theriogenology.2017.06.013","article-title":"Peroxisome proliferator-activated receptor (PPAR) isoforms are differentially expressed in peri-implantation porcine conceptuses","volume":"101","author":"Blitek","year":"2017","journal-title":"Theriogenology."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20210469","article-title":"Eosinophils are part of the granulocyte response in tuberculosis and promote host resistance in mice","volume":"218","author":"Bohrer","year":"2021","journal-title":"J. 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