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:170-2</font></em></font></strong></font></td></tr><tr><td colspan=2><br><br><table align=center width=700><tr><td><b>Poster (Painel)</b><br><table width="100%"><tr><td width="60">170-2</td><td><b>INFLUENCE OF THE HOST GENETIC BACKGROUND ON CYTOKINES EXPRESSION IN GRANULOMATOUS LESIONS OF P. BRASILIENSIS-INOCULATED INBRED MICE</b></td></tr><tr><td valign=top>Authors:</td><td><u>Eva Burger </u> (USP - Universidade de Sao Paulo) ; Angela Satie Nishikaku (USP - Universidade de Sao PauloUNIFESP - Universidade Federal de Sao Paulo) ; Jose Vicente Alves (USP - Universidade de Sao Paulo) ; Raphael Fagnani Sanches Molina (USP - Universidade de Sao Paulo) ; Jacy Gameiro (UNICAMP - Universidade Estadual de Campinas) ; Cf Andrade (UNICAMP - Universidade Estadual de Campinas) ; Dagmar Stach-machado (UNICAMP - Universidade Estadual de Campinas) ; Zoilo Pires de Camargo (UNIFESP - Universidade Federal de Sao Paulo) ; Liana Verinaud (UNICAMP - Universidade Estadual de Campinas) </td></tr></table><p align=justify><b><font size=2>Abstract</font></b><p align=justify class=tres><font size=2>The severe clinical forms of paracoccidioidomycosis present numerous granulomatous lesions and anergy in protective cellular immunity; in contrast, mild forms show few localized granulomas and preserved cellular immune response. This pattern can be reproduced by infecting susceptible (S) and resistant (R) mice with a virulent P. brasiliensis (Pb) isolate so allowing the comparison of the granulomas architecture, areas of lesions comprising Pb with preserved or altered morphology, and the presence and distribution of different cell populations, extracellular matrix components cytokines. Regarding these later components we studied relevant cytokines to granuloma formation and host-fungal interactions by determining their concentration in organ supernatant by ELISA, the expression of their mRNAs by RT-PCR and their localization by immunohistochemistry and compared the lesions developed in the omentum of S and R mice to detect eventual differences due to the genetic background of the mice. The total areas of lesions as well as the percentage of these lesions occupied by Pb were significantly higher in S than in R mice, in parallel with the higher viable fungal loads in the former strain. The local production of stimulatory cytokines TNF-a and g-IFN was always higher in the R strain than in the S one; in contrast, the inhibitory cytokine TGF-b was detected in lower concentrations in the omental tissue of R mice than in those of the S mice, as indicated by the areas of positive imunohistochemical reactions. RT-PCR revealed an 8X higher expression of IFN-&#947; mRNA and an 11X higher expression of TNF-&#945; mRNA in R than in S strain and immunohistochemistry showed that the number of IFN-&#947; cells was 2.5X higher in R than in S mice. However, TNF-&#945; positivity was similar in the granulomas of S and R mice. TGF-&#946; and IL-10 mRNAs were respectively 1.2 and 1.0 more expressed in S than in R mice and there were 1.2X more TGF-&#946; cells in the former strain. The total area of granulomatous lesions and the relative areas of lesions containing Pb were respectively 1.2X and 1.9X more extensive in S mice than in the R ones. ELISA of omentum homogenates also revealed high production of regulatory IL-10 and TGF-&#946; cytokines and low levels of stimulatory cytokines TNF-a and g-IFN. Therefore, infection of R mice by a virulent Pb strain leads to the preferential synthesis of mRNAs and of proteins of TNF-&#945; and IFN-&#947; that promote macrophage activation, probably enhancing Pb killing and control of fungal dissemination in parallel with development of small granulomatous lesions containing few fungi; whereas infection of S mice elicits preferential synthesis of mRNAs and protein of TGF-&#946; and IL-10 which deactivate macrophages and may inhibit Pb killing by macrophages, favoring fungal dissemination and formation of bigger granulomatous lesions. SUPPORT: FAPESP # 06/60091-6 & # 08/58604-0; CNPq 304630/2009-8 </font></p><br><b>Keyword: </b>&nbsp;susceptibility and resistance, granulomatous lesions, cytokines</td></tr></table></tr></td></table></body></html>