25º Congresso Brasileiro de Microbiologia
ResumoID:1414-1


Área: Imunologia ( Divisão E )

TG MIC1 AND TG MIC4 MICRONEMAL PROTEINS OF T.GONDII REGULATES PARASITE-INDUCED IL-12 PRODUCTION BY ANTIGEN PRESENTING CELLS

Camila Figueiredo Pinzan (FMRP); Elaine Vicente Lourenço (FMRP); Maria Cristina Roque Antunes Barreira (FMRP)

Resumo

Introduction and Objectives: Microneme discharge is the first step in host invasion and the binding of micronemal proteins to host cells provides a molecular bridge to the parasite, thereby facilitating further steps of invasion. TgMIC1 and TgMIC4 are micronemes proteins that constitute a lactose-binding fraction (Lac+) purified from soluble tachyzoites antigen (STAg) of T. gondii. Host resistance to the intracellular protozoan Toxoplasma gondii is highly dependent on early IL-12 production by APC.Crude STAg was recently demonstrated as a potent inducer of IL-12 production by dendritic cells (DC), an activity presumably due to antigen interaction with TLR(s) on DC surface (Immunol Rev.201:26-34, 2004). Considering that the active STAg component(s) was not identified and lectins are potential ligands for TLRs, in this work, we evaluated if Lac+ fraction and MIC1 and MIC4 recombinant proteins can account for the IL-12 induction by different antigen presenting cells. Methods and Results: To examine if LAC+ induces IL-12 responsiveness in one or more cell types, highly enriched bone marrow-derived neutrophils, splenic dendritic cells and thioglycolate-elicited peritoneal macrophages were stimulated in vitro with 1g/ml of these proteins and IL-12p40 production was measured by ELISA. The LAC+ fraction induced high levels of IL-12 production by all cell types tested ( 972, 1790, 1100 pg/ml respectively). Moreover, the IL-12 production was significantly reduced by addition of of 0,05M lactose in cocultures showing that this characteristic was dependent on the lectin carbohydrate-recognition domain. These results suggest that IL-12 production is induced by TgMIC1 and TgMIC4 proteins that constitutes the LAC+ fraction. In order to unambiguously attribute this activity for these lectins we prepared both recombinant proteins. Our results showed that IL-12 responsiveness was also greatly induced in neutrophils, macrophages and dendritc cells stimulated in vitro with these recombinant micronemal proteins. Conclusion: Taken together, these data suggest that the micromemal lectins TgMIC1 and TgMIC4 from T. gondii induces APCs to release IL-12, a property that is possibly due to the TgMIC1/4/6 parasite complex in the nature. ਀䘀椀渀愀渀挀椀愀氀 猀甀瀀瀀漀爀琀㨀 䘀䄀倀䔀匀倀Ⰰ 䘀䄀䔀倀䄀⸀㰀⼀昀漀渀琀㸀㰀⼀瀀㸀㰀戀爀㸀㰀戀㸀倀愀氀愀瘀爀愀猀ⴀ挀栀愀瘀攀㨀 㰀⼀戀㸀☀渀戀猀瀀㬀䄀渀琀椀最攀渀 倀爀攀猀攀渀琀椀渀最 䌀攀氀氀猀Ⰰ 䌀礀琀漀欀椀渀攀Ⰰ 䰀攀挀琀椀渀Ⰰ 吀漀砀漀瀀氀愀猀洀愀 最漀渀搀椀椀㰀⼀琀搀㸀㰀⼀琀爀㸀㰀⼀琀愀戀氀攀㸀㰀⼀琀爀㸀㰀⼀琀搀㸀㰀⼀琀愀戀氀攀㸀㰀⼀戀漀搀礀㸀㰀⼀栀琀洀氀㸀