{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:47:04Z","timestamp":1791190024095,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2008,3,1]],"date-time":"2008-03-01T00:00:00Z","timestamp":1204329600000},"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":[[2008,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Paracoccidioidomycosis, a debilitating pulmonary mycosis, is caused by the dimorphic fungus Paracoccidioides brasiliensis. The infection results in the formation of granulomas containing viable yeast cells that are the fungal sources for disease reactivation. Because CD4+CD25+ regulatory T cells (Tregs) are in the lesions of patients with paracoccidioidomycosis, the migration of Treg cells is dependent on the axis chemokine-chemokine receptors, and CCR5 ligands are produced in P. brasiliensis-induced lesions, we investigated the role of CCR5 in the control of the infection. The results showed that CCR5\u2212\/\u2212 mice are more efficient in controlling fungal growth and dissemination and exhibited smaller granulomas than wild-type (WT) mice. In the absence of CCR5, the percentage of CD4+CD25+ T cells expressing Foxp3, glucocorticoid-induced TNFR (GITR), CD103, CD45low, and CTLA-4 in the granulomas was significantly decreased. Interestingly, P. brasiliensis infection resulted in an absence of T cell proliferation in response to Con A in WT but not CCR5\u2212\/\u2212 mice that was abrogated by anti-CTLA-4 mAb and anti-GITR mAb. Moreover, the adoptive transfer of CD4+CD25+ but not CD4+CD25\u2212 T cells from infected WT to infected CCR5\u2212\/\u2212 mice resulted in a significant increase in fungal load. Overall, CCR5 is a key receptor for the migration of Treg cells to the site of P. brasiliensis infection, leading to down-modulation of effector immune response and the long-term presence of the fungus in the granulomas. Thus, a tight control of Treg cell migration to the granulomatous lesions could be an important mechanism for avoiding exacerbation and reactivation of the disease.<\/jats:p>","DOI":"10.4049\/jimmunol.180.5.3049","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:16:52Z","timestamp":1397848612000},"page":"3049-3056","source":"Crossref","is-referenced-by-count":74,"title":["CCR5-Dependent Regulatory T Cell Migration Mediates Fungal Survival and Severe Immunosuppression"],"prefix":"10.1093","volume":"180","author":[{"given":"Ana Paula","family":"Moreira","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Immunology, Universidade de Sa\u0303o Paulo , Sa\u0303o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen Angelica","family":"Cavassani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Universidade de Sa\u0303o Paulo , Sa\u0303o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrine Sales Massafera","family":"Trista\u0303o","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Universidade de Sa\u0303o Paulo , Sa\u0303o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula","family":"Campanelli","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Universidade de Sa\u0303o Paulo , Sa\u0303o Paulo ,","place":["Brazil"]},{"name":"Department of Biological Sciences, Bauru Dental School, Universidade de Sa\u0303o Paulo , Sa\u0303o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department Internal Medicine, Universidade de Sa\u0303o Paulo , Sa\u0303o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos Antonio","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine of Ribeira\u0303o Preto, Universidade de Sa\u0303o Paulo , Sa\u0303o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joa\u0303o S","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Universidade de Sa\u0303o Paulo , Sa\u0303o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,3,1]]},"reference":[{"key":"2026012809405783000_R1","first-page":"89","volume-title":"Clin. Microbiol. Rev.","year":"1993"},{"key":"2026012809405783000_R2","first-page":"139","volume-title":"Microbes Infect.","year":"2002"},{"key":"2026012809405783000_R3","first-page":"765","volume-title":"Trans. R. Soc. Trop. Med. Hyg.","year":"1985"},{"key":"2026012809405783000_R4","first-page":"1270","volume-title":"Am. J. Pathol.","year":"2006"},{"key":"2026012809405783000_R5","first-page":"1811","volume-title":"Am. J. Pathol.","year":"2000"},{"key":"2026012809405783000_R6","first-page":"149","volume-title":"Cytokine","year":"2002"},{"key":"2026012809405783000_R7","first-page":"583","volume-title":"Am. J. Pathol.","year":"2003"},{"key":"2026012809405783000_R8","first-page":"800","volume-title":"Infect. Immun.","year":"1998"},{"key":"2026012809405783000_R9","first-page":"248","volume-title":"Cytokine","year":"2001"},{"key":"2026012809405783000_R10","first-page":"1496","volume-title":"J. Infect. Dis.","year":"2003"},{"key":"2026012809405783000_R11","first-page":"5811","volume-title":"J. Immunol.","year":"2006"},{"key":"2026012809405783000_R12","first-page":"1037","volume-title":"J. Exp. Med.","year":"2005"},{"key":"2026012809405783000_R13","first-page":"942","volume-title":"Nat. Med.","year":"2004"},{"key":"2026012809405783000_R14","first-page":"847","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2026012809405783000_R15","first-page":"3300","volume-title":"Blood","year":"2005"},{"key":"2026012809405783000_R16","first-page":"632","volume-title":"Trends Immunol.","year":"2005"},{"key":"2026012809405783000_R17","first-page":"1126","volume-title":"Nat. Immunol.","year":"2001"},{"key":"2026012809405783000_R18","first-page":"21","volume-title":"Clin. Immunol. Immunopathol.","year":"1979"},{"key":"2026012809405783000_R19","first-page":"123","volume-title":"Nat. Immunol.","year":"2001"},{"key":"2026012809405783000_R20","first-page":"627","volume-title":"J. Infect. Dis.","year":"2005"},{"key":"2026012809405783000_R21","first-page":"491","volume-title":"Gastroenterology","year":"2003"},{"key":"2026012809405783000_R22","first-page":"391","volume-title":"Med. Mycol.","year":"2003"},{"key":"2026012809405783000_R23","first-page":"4593","volume-title":"J. Immunol.","year":"2002"},{"key":"2026012809405783000_R24","first-page":"20","volume-title":"Cytokine","year":"2005"},{"key":"2026012809405783000_R25","first-page":"2451","volume-title":"J. Exp. Med.","year":"2006"},{"key":"2026012809405783000_R26","first-page":"594","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2007"},{"key":"2026012809405783000_R27","first-page":"966","volume-title":"Gastroenterology","year":"2007"},{"key":"2026012809405783000_R28","first-page":"374","volume-title":"Trends Immunol.","year":"2004"},{"key":"2026012809405783000_R29","first-page":"108","volume-title":"Trends Mol. Med.","year":"2007"},{"key":"2026012809405783000_R30","first-page":"330","volume-title":"Nat. Immunol.","year":"2003"},{"key":"2026012809405783000_R31","first-page":"201","volume-title":"J. Exp. Med.","year":"2004"},{"key":"2026012809405783000_R32","first-page":"287","volume-title":"Immunity","year":"2005"},{"key":"2026012809405783000_R33","first-page":"1263","volume-title":"J. Infect. Dis.","year":"1997"},{"key":"2026012809405783000_R34","first-page":"613","volume-title":"Nat. Rev. Immunol.","year":"2006"},{"key":"2026012809405783000_R35","first-page":"1057","volume-title":"Science","year":"2003"},{"key":"2026012809405783000_R36","first-page":"305","volume-title":"Nat. Rev. Immunol.","year":"2007"},{"key":"2026012809405783000_R37","first-page":"457","volume-title":"Nat. Immunol.","year":"2007"},{"key":"2026012809405783000_R38","first-page":"277","volume-title":"Nat. Immunol.","year":"2007"},{"key":"2026012809405783000_R39","first-page":"771","volume-title":"Nature","year":"2007"},{"key":"2026012809405783000_R40","first-page":"36828","volume-title":"J. Biol. Chem.","year":"2006"},{"key":"2026012809405783000_R41","first-page":"5138","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2005"},{"key":"2026012809405783000_R42","first-page":"253","volume-title":"Cell","year":"2006"},{"key":"2026012809405783000_R43","first-page":"375","volume-title":"Cell","year":"2006"},{"key":"2026012809405783000_R44","first-page":"149","volume-title":"Immunol. Rev.","year":"2006"},{"key":"2026012809405783000_R45","first-page":"287","volume-title":"Immunol. Rev.","year":"2006"},{"key":"2026012809405783000_R46","first-page":"447","volume-title":"Immunology","year":"2007"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/180\/5\/3049\/62677434\/zim00508003049.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/180\/5\/3049\/62677434\/zim00508003049.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T14:41:05Z","timestamp":1769611265000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/180\/5\/3049\/8023504"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,3,1]]},"references-count":46,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2008,3,1]]},"published-print":{"date-parts":[[2008,3,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.180.5.3049","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2008,3]]},"published":{"date-parts":[[2008,3,1]]}}}