{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T05:45:10Z","timestamp":1741153510033,"version":"3.38.0"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Granuloma formation is a hallmark of several infectious diseases, including those caused by Mycobacterium sp. These structures are composed of accumulations of inflammatory cells, and it has been shown that cytokines such as IFN-\u03b3 and TNF-\u03b1 are required for granuloma assembly during M. avium infections in mice. Macrophages (M\u03a6s) insensitive to IFN-\u03b3 (MIIG) mice have M\u03a6s, monocytes, and dendritic cells that are unresponsive to IFN-\u03b3. We observed that although IFN-\u03b3\u2212\/\u2212 mice present an exacerbated infection, the same is not true for MIIG animals, where the same levels of protection as the wild-type animals were observed in the liver and partial protection in the spleen. Unlike IFN-\u03b3\u2212\/\u2212 mice, MIIG mice still develop well-defined granulomas, suggesting that IFN-\u03b3\u2013mediated M\u03a6 activation is not required for granuloma assembly. This work also shows that MIIG animals exhibit increased cell recruitment with higher CD4+ T cells numbers as well as increased IFN-\u03b3 and TNF-\u03b1 expression, suggesting that TNF-\u03b1 may have a role in protection and may compensate the lack of M\u03a6 response to IFN-\u03b3 in the MIIG model. TNF-\u03b1\u2013deficient MIIG mice (MIIG.TNF-\u03b1\u2212\/\u2212) exhibited increased bacterial burdens when compared with MIIG mice. These results suggest that in the absence of IFN-\u03b3 signaling in M\u03a6s, TNF-\u03b1 has a protective role against M. avium.<\/jats:p>","DOI":"10.4049\/jimmunol.1801594","type":"journal-article","created":{"date-parts":[[2019,9,28]],"date-time":"2019-09-28T00:06:18Z","timestamp":1569629178000},"page":"2451-2458","source":"Crossref","is-referenced-by-count":5,"title":["TNF-Mediated Compensatory Immunity to <i>Mycobacterium avium<\/i> in the Absence of Macrophage Activation by IFN-\u03b3"],"prefix":"10.1093","volume":"203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4835-3035","authenticated-orcid":false,"given":"Mariana","family":"Resende","sequence":"first","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto , 4200-135 Porto ,","place":["Portugal"]},{"name":"IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto , 4200-135 Porto ,","place":["Portugal"]},{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho , 4710-057 Braga ,","place":["Portugal"]},{"name":"ICVS\/3B\u2019s \u2013 PT Government Associate Laboratory, University of Minho , 4710-057 Braga ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0150-7359","authenticated-orcid":false,"given":"Marcos S","family":"Cardoso","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto , 4200-135 Porto ,","place":["Portugal"]},{"name":"IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto , 4200-135 Porto ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7338-2383","authenticated-orcid":false,"given":"Ricardo","family":"Fr\u00f3is-Martins","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto , 4200-135 Porto ,","place":["Portugal"]},{"name":"IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto , 4200-135 Porto ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6035-4095","authenticated-orcid":false,"given":"Margarida","family":"Borges","sequence":"additional","affiliation":[{"name":"IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto , 4200-135 Porto ,","place":["Portugal"]}]},{"given":"Michael B","family":"Jordan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cincinnati Children\u2019s Hospital Medical Center\/University of Cincinnati College of Medicine , Cincinnati, OH 45229"}]},{"given":"Ant\u00f3nio Gil","family":"Castro","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho , 4710-057 Braga ,","place":["Portugal"]},{"name":"ICVS\/3B\u2019s \u2013 PT Government Associate Laboratory, University of Minho , 4710-057 Braga ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9447-0665","authenticated-orcid":false,"given":"Rui","family":"Appelberg","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto , 4200-135 Porto ,","place":["Portugal"]},{"name":"IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto , 4200-135 Porto ,","place":["Portugal"]},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas de Abel Salazar, Universidade do Porto , 4050-313 Porto ,","place":["Portugal"]}]}],"member":"286","published-online":{"date-parts":[[2019,11,1]]},"reference":[{"key":"2025030417543752700_r1","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1084\/jem.158.3.670","article-title":"Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity","volume":"158","author":"Nathan","year":"1983","journal-title":"J. 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