ÿþ<HTML><HEAD><TITLE>XI International Meeting on Paracoccidioidomycosis</TITLE><link rel=STYLESHEET type=text/css href=css.css></HEAD><BODY aLink=#ff0000 bgColor=#FFFFFF leftMargin=0 link=#000000 text=#000000 topMargin=0 vLink=#000000 marginheight=0 marginwidth=0><table align=center width=700 cellpadding=0 cellspacing=0><tr><td align=left bgcolor=#cccccc valign=top width=550><font face=arial size=2><strong><font face=Verdana, Arial, Helvetica, sans-serif size=3><font size=1>XI International Meeting on Paracoccidioidomycosis</font></font></strong><font face=Verdana size=1><b><br></b></font><font face=Verdana, Arial,Helvetica, sans-serif size=1><strong> </strong></font></font></td><td align=right bgcolor=#cccccc valign=top width=150><font face=arial size=2><strong><font face=Verdana, Arial, Helvetica, sans-serif size=1><font size=1>Resume:167-1</font></em></font></strong></font></td></tr><tr><td colspan=2><br><br><table align=center width=700><tr><td><b>Investigação</b><br><table width="100%"><tr><td width="60">167-1</td><td><b>N-Glycans from TLR2 heterodimers as targets for a lectin that confers protection against paracoccidiodomycosis</b></td></tr><tr><td valign=top>Authors:</td><td><u>Maria Cristina Roque Barreira </u> (FMRP- USP - Faculdade de Medicina de Ribeirão Preto- USP) </td></tr></table><p align=justify><b><font size=2>Abstract</font></b><p align=justify class=tres><font size=2>ArtinM, a D-mannose binding lectin, confers resistance to experimental infections with Paracoccidioides brasiliensis. ArtinM-treated mice, in comparison to the non-treated ones, show lower fungal burden in their organs, higher production of IL-12, IFN-gamma and TNF-alpha. The host advantageous effects provided by ArtinM are not verified in IL-12 KO mice. Murine macrophages stimulated with ArtinM produce high IL-12 levels, a response that is not verified when the cells were derived from MyD88 KO mice or in the presence of D-mannose. The role of Toll-like receptors in the macrophage response was delineated in ArtinM-stimulated macrophages from TLR2- and TLR4-deficient mice; the IL-12 production was blocked only in the cells from TLR-2 KO mice. The facts that the TLR2 ectodomain has 4 N-glycans and that ArtinM recognizes specifically the trimannoside core of N-glycans explain the lectin interaction with the PRR. The ArtinM stimulus of HEK 293 cells transfected with plasmids coupled with the TLR-2 ectodomain and a NF-kB-luciferase reporter gene promoted NFkB translocation, which was not verified when ArtinM was pre-incubated with the D-mannose or was used to stimulate TLR4 transfected cells. To better understand the mechanisms responsible for the ArtinM immunomodulatory effect in PCM, the HEK293 cells were also transfected with TLR2 heterodimers (TLR2/1 and TLR2/6), as well as with coreceptors/ accessory molecules (CD36, CD14, MD-2). The ArtinM stimulus promoted NF-kB activation in cells expressing TLR2/1 and TLR2/6. No activation was determined by similar AM concentrations in cells expressing TLR4. The co-receptor CD36 was shown to be especially important in the process, because in its absence concentrations 10 times higher of ArtinM were required to induce NF-kB activation. The exact role exerted by the scavenger glycosylated receptor CD36 on the signaling triggered by ArtinM is under investigation. </font></p><br><b>Keyword: </b>&nbsp;immunomodulation, Toll-like receptor, N-glycan, lectin, Th1 immunity</td></tr></table></tr></td></table></body></html>