{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T19:34:33Z","timestamp":1791056073581,"version":"4.1.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2003,3,1]],"date-time":"2003-03-01T00:00:00Z","timestamp":1046476800000},"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":[[2003,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>TGF-\u03b2 is a potent regulatory cytokine that suppresses expression of inducible NO synthase and IFN-\u03b3, and suppresses Th1 and Th2 cell development. We examined whether functionally active TGF-\u03b2 is present in the local environment surrounding the invading protozoan Leishmania chagasi. Our prior data showed that TGF-\u03b2 levels are significantly increased in L. chagasi-infected mice. In the current study, we found TGF-\u03b2 was also abundant in bone marrows of humans with acute visceral leishmaniasis but not in those of uninfected controls. Furthermore, L. chagasi infection caused an increase in biologically active TGF-\u03b2 in human macrophage cultures without changing the total TGF-\u03b2. Therefore, we investigated the means through which leishmania could augment activated but not total TGF-\u03b2. Incubation of latent TGF-\u03b2 with Leishmania sp. promastigotes caused active TGF-\u03b2 to be released from the latent complex. In contrast, the nonpathogenic protozoan Crithidia fasciculata could not activate TGF-\u03b2. TGF-\u03b2 activation by leishmania was prevented by inhibitors of cysteine proteases and by the specific cathepsin B inhibitor CA074. Physiologic concentrations of TGF-\u03b2 inhibited killing of intracellular L. chagasi in macrophages, although the phagocytosis-induced respiratory burst remained intact. In contrast, supraphysiologic concentrations of TGF-\u03b2 had no effect on parasite survival. We hypothesize that the combined effect of abundant TGF-\u03b2 stores at extracellular sites during infection, and the ability of the parasite to activate TGF-\u03b2 in its local environment, leads to high levels of active TGF-\u03b2 in the vicinity of the infected macrophage. Locally activated TGF-\u03b2 could, in turn, enhance parasite survival through its effects on innate and adaptive immune responses.<\/jats:p>","DOI":"10.4049\/jimmunol.170.5.2613","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:32:44Z","timestamp":1398029564000},"page":"2613-2620","source":"Crossref","is-referenced-by-count":140,"title":["Activation of TGF-\u03b2 by\n                    <i>Leishmania chagasi<\/i>\n                    : Importance for Parasite Survival in Macrophages"],"prefix":"10.1093","volume":"170","author":[{"given":"Kira R","family":"Gantt","sequence":"first","affiliation":[{"name":"Interdisciplinary Immunology PhD Program, University of Iowa , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey","family":"Schultz-Cherry","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin , Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilda","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Iowa , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selma M B","family":"Jeronimo","sequence":"additional","affiliation":[{"name":"Departamento de Bioquimica, Universidade Federal do Rio Grande do Norte , Natal, RN ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana T","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Departamento de Bioquimica, Universidade Federal do Rio Grande do Norte , Natal, RN ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd L","family":"Goldman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa , Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J","family":"Recker","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs Medical Center , Iowa City, IA 52240"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs Medical Center , Iowa City, IA 52240"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E","family":"Wilson","sequence":"additional","affiliation":[{"name":"Interdisciplinary Immunology PhD Program, University of Iowa , Iowa City, IA 52242"},{"name":"Department of Internal Medicine, University of Iowa , Iowa City, IA 52242"},{"name":"Department of Microbiology, University of Iowa , Iowa City, IA 52242"},{"name":"Department of Veterans Affairs Medical Center , Iowa City, IA 52240"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,3,1]]},"reference":[{"key":"2026020210101124900_R1","first-page":"1","volume-title":"Clin. Infect. Dis.","year":"1996"},{"key":"2026020210101124900_R2","first-page":"974","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020210101124900_R3","first-page":"545","volume-title":"Science","year":"1992"},{"key":"2026020210101124900_R4","first-page":"1912","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020210101124900_R5","first-page":"6148","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020210101124900_R6","first-page":"1233","volume-title":"Infect. Immun.","year":"1998"},{"key":"2026020210101124900_R7","first-page":"1499","volume-title":"J. Exp. Med.","year":"2002"},{"key":"2026020210101124900_R8","first-page":"D1171","volume-title":"Front. Biosci.","year":"1998"},{"key":"2026020210101124900_R9","first-page":"2001","volume-title":"J. Immunol.","year":"2000"},{"key":"2026020210101124900_R10","first-page":"3442","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1993"},{"key":"2026020210101124900_R11","first-page":"1376","volume-title":"Kidney Int.","year":"1997"},{"key":"2026020210101124900_R12","first-page":"2077","volume-title":"J. Immunol.","year":"1995"},{"key":"2026020210101124900_R13","first-page":"713","volume-title":"Ann. NY Acad. Sci.","year":"1993"},{"key":"2026020210101124900_R14","first-page":"893","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020210101124900_R15","first-page":"4681","volume-title":"J. Immunol.","year":"1986"},{"key":"2026020210101124900_R16","first-page":"33883","volume-title":"J. Biol. Chem.","year":"2000"},{"key":"2026020210101124900_R17","first-page":"8624","volume-title":"J. Virol.","year":"1996"},{"key":"2026020210101124900_R18","first-page":"276","volume-title":"Anal. Biochem.","year":"2000"},{"key":"2026020210101124900_R19","first-page":"9098","volume-title":"J. Biol. Chem.","year":"1986"},{"key":"2026020210101124900_R20","first-page":"113","volume-title":"Biochem. J.","year":"1999"},{"key":"2026020210101124900_R21","first-page":"1450","volume-title":"J. Immunol.","year":"1995"},{"key":"2026020210101124900_R22","first-page":"399","volume-title":"Infect. Immun.","year":"2002"},{"key":"2026020210101124900_R23","first-page":"4020","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020210101124900_R24","first-page":"7483","volume-title":"J. Biol. Chem.","year":"1989"},{"key":"2026020210101124900_R25","first-page":"197","volume-title":"Mol. Biochem. Parasitol.","year":"1986"},{"key":"2026020210101124900_R26","first-page":"635","volume-title":"J. Biochem. (Tokyo)","year":"2000"},{"key":"2026020210101124900_R27","first-page":"377","volume-title":"Arch. Biochem. Biophys.","year":"1992"},{"key":"2026020210101124900_R28","first-page":"25305","volume-title":"J. Biol. Chem.","year":"2002"},{"key":"2026020210101124900_R29","first-page":"18","volume-title":"Parasitol. Today","year":"2000"},{"key":"2026020210101124900_R30","first-page":"142","volume-title":"Br. J. Biomed. Sci.","year":"1995"},{"key":"2026020210101124900_R31","first-page":"137","volume-title":"Annu. Rev. Immunol.","year":"1998"},{"key":"2026020210101124900_R32","first-page":"3462","volume-title":"J. Immunol.","year":"1989"},{"key":"2026020210101124900_R33","first-page":"255","volume-title":"J. Pharmacol. Exp. Ther.","year":"1991"},{"key":"2026020210101124900_R34","first-page":"123","volume-title":"Histochem. J.","year":"1998"},{"key":"2026020210101124900_R35","first-page":"3926","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1997"},{"key":"2026020210101124900_R36","first-page":"1847","volume-title":"J. Infect. Dis.","year":"1998"},{"key":"2026020210101124900_R37","first-page":"401","volume-title":"J. Leukocyte Biol.","year":"1994"},{"key":"2026020210101124900_R38","first-page":"487","volume-title":"Trends Parasitol.","year":"2001"},{"key":"2026020210101124900_R39","first-page":"6805","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1991"},{"key":"2026020210101124900_R40","first-page":"5788","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1987"},{"key":"2026020210101124900_R41","first-page":"1600","volume-title":"J. Immunol.","year":"1991"},{"key":"2026020210101124900_R42","first-page":"609","volume-title":"J. Immunol.","year":"1991"},{"key":"2026020210101124900_R43","first-page":"1587","volume-title":"J. Exp. Med.","year":"1994"},{"key":"2026020210101124900_R44","first-page":"605","volume-title":"J. Exp. Med.","year":"1993"},{"key":"2026020210101124900_R45","first-page":"667","volume-title":"Biochem. Biophys. Res. Commun.","year":"1995"},{"key":"2026020210101124900_R46","first-page":"777","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2026020210101124900_R47","first-page":"2930","volume-title":"J. Immunol.","year":"1994"},{"key":"2026020210101124900_R48","first-page":"2187","volume-title":"Endocrinology","year":"1993"},{"key":"2026020210101124900_R49","first-page":"1355","volume-title":"Kidney Int.","year":"1997"},{"key":"2026020210101124900_R50","first-page":"14829","volume-title":"J. Biol. Chem.","year":"2002"},{"key":"2026020210101124900_R51","first-page":"348","volume-title":"Cytokine","year":"1999"},{"key":"2026020210101124900_R52","first-page":"271","volume-title":"Mol. Biochem. Parasitol.","year":"1993"},{"key":"2026020210101124900_R53","first-page":"220","volume-title":"Parasitol. Today","year":"1998"},{"key":"2026020210101124900_R54","first-page":"257","volume-title":"Gene","year":"2001"},{"key":"2026020210101124900_R55","first-page":"53","volume-title":"Mol. Biochem. Parasitol.","year":"1997"},{"key":"2026020210101124900_R56","first-page":"367","volume-title":"Parasitology","year":"2000"},{"key":"2026020210101124900_R57","first-page":"271","volume-title":"Mol. Biochem. Parasitol.","year":"1995"},{"key":"2026020210101124900_R58","first-page":"6794","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020210101124900_R59","first-page":"2120","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020210101124900_R60","first-page":"43","volume-title":"Mol. Biochem. Parasitol.","year":"1988"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/170\/5\/2613\/62567311\/2613.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/170\/5\/2613\/62567311\/2613.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T15:13:05Z","timestamp":1770045185000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/170\/5\/2613\/8028436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,3,1]]},"references-count":60,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2003,3,1]]},"published-print":{"date-parts":[[2003,3,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.170.5.2613","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2003,3]]},"published":{"date-parts":[[2003,3,1]]}}}