{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T20:06:01Z","timestamp":1778270761736,"version":"3.51.4"},"reference-count":65,"publisher":"Rockefeller University Press","issue":"12","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,12,20]]},"abstract":"<jats:p>The Trypanosoma cruzi trans-sialidase can sensitize mice to become highly susceptible to T. cruzi invasion, through mechanisms that remain unknown. In pursuing this observation, we found that purified trans-sialidase induces the selective release of biologically active interleukin (IL)-6 in naive human intestinal microvascular endothelial cells (HIMECs), peripheral blood mononuclear cells (PBMCs), and bladder carcinoma cells. The trans-sialidase action was independent of its catalytic activity, as demonstrated with a genetically engineered trans-sialidase mutant, an enzymatically active polypeptide, and cocultures of PBMCs with epimastigotes and trypomastigotes. Instead, the trans-sialidase action was reproduced with a recombinant COOH-terminal tandem repeat and with synthetic peptides modeled on the tandem repeat. Most interesting, HIMECs infected with a trypomastigote population expressing trans-sialidase effectively released IL-6, but did not upon infection with the counterpart trypomastigote population expressing low trans-sialidase levels. IL-6 is a key factor in the regulation and symptom formation of infection caused by several types of viruses, such as HIV and influenza A virus. However, the function of IL-6 in protozoan and other parasitic diseases remains unclear. The unique findings presented here suggest that trans-sialidase is a major inducer of IL-6 secretion in T. cruzi infection, independently of immune cell activation. Such IL-6 secretion might underlie some features of Chagas's disease, such as pyrexia, neuroprotection, and fibrosis, and might result in the undermining of normal acquired immunity against T. cruzi.<\/jats:p>","DOI":"10.1084\/jem.190.12.1825","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"1825-1836","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":45,"title":["The <i>Trypanosoma cruzi trans<\/i>-Sialidase, through Its Cooh-Terminal Tandem Repeat, Upregulates Interleukin 6 Secretion in Normal Human Intestinal Microvascular Endothelial Cells and Peripheral Blood Mononuclear Cells"],"prefix":"10.1084","volume":"190","author":[{"given":"Emma","family":"Saavedra","sequence":"first","affiliation":[{"name":"aParasitology Research Center, Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Macario","family":"Herrera","sequence":"additional","affiliation":[{"name":"aParasitology Research Center, Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenda","family":"Gao","sequence":"additional","affiliation":[{"name":"aParasitology Research Center, Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruki","family":"Uemura","sequence":"additional","affiliation":[{"name":"bInstitute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miercio A.","family":"Pereira","sequence":"additional","affiliation":[{"name":"aParasitology Research Center, Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1999,12,20]]},"reference":[{"key":"2023072508523076100_R1","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1093\/infdis\/166.3.598","article-title":"Cytokine gene expression of endothelial cells infected with Trypanosoma cruzi","volume":"166","author":"Tanowitz","year":"1992","journal-title":"J. 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