Abstract

Introduction and objectives: IL-18 is a proinflammatory cytokine and its role in paracoccidioidomycosis, a deep਀洀礀挀漀猀椀猀Ⰰ 椀猀 渀漀琀 昀甀氀氀礀 甀渀搀攀爀猀琀漀漀搀⸀ 吀栀攀 攀昀昀攀挀琀 漀昀 䤀䰀ⴀ㄀㠀 漀渀 洀漀渀漀挀礀琀攀 愀挀琀椀瘀椀琀礀 愀最愀椀渀猀琀 倀⸀ 戀爀愀猀椀氀椀攀渀猀椀猀 ⠀倀戀⤀ 眀愀猀 猀琀甀搀椀攀搀 戀礀 evaluating the fungicidal activity, H2O2 production, the modulation of TLR2, TLR4 and mannose receptor (MR)਀攀砀瀀爀攀猀猀椀漀渀Ⰰ 愀渀搀 䤀䰀ⴀ㄀㠀Ⰰ 䤀䰀ⴀ㄀　Ⰰ 吀一䘀ⴀ☀⌀㤀㐀㔀㬀Ⰰ 䤀䰀ⴀ㄀㈀ 愀渀搀 䤀䰀ⴀ㄀㔀 瀀爀漀搀甀挀琀椀漀渀 愀昀琀攀爀 挀栀愀氀氀攀渀最攀 椀渀 瘀椀琀爀漀 眀椀琀栀 昀甀渀最甀猀⸀ 䴀攀琀栀漀搀猀㨀 䴀漀渀漀挀礀琀攀猀 were stimulated with IL-18 and treated with anti-TLR2, anti-TLR4, anti-CD14 and/or anti-MR before challenge with Pb18਀⠀瘀椀爀甀氀攀渀琀⤀ 愀渀搀 倀戀㈀㘀㔀 ⠀愀瘀椀爀甀氀攀渀琀⤀⸀ 䘀甀渀最愀氀 爀攀挀漀瘀攀爀礀 愀渀搀 䠀㈀伀㈀ 瀀爀漀搀甀挀琀椀漀渀 眀攀爀攀 愀猀猀攀猀猀攀搀⸀ 吀䰀刀㈀Ⰰ 吀䰀刀㐀Ⰰ 䴀刀 愀渀搀 䌀䐀㄀㐀 expression were analyzed by flow cytometry and IL-18, IL-10, TNF-α, IL-12 and IL-15 production were analyzed by ELISA and by flow cytometry. Results: The਀爀攀猀甀氀琀猀 猀栀漀眀攀搀 琀栀愀琀 䤀䰀ⴀ㄀㠀 椀渀挀爀攀愀猀攀搀 昀甀渀最愀氀 爀攀挀漀瘀攀爀礀 昀爀漀洀 椀渀昀攀挀琀攀搀 洀漀渀漀挀礀琀攀猀 愀渀搀 琀栀攀 戀氀漀挀欀愀最攀 漀昀 爀攀挀攀瀀琀漀爀猀 眀椀琀栀 猀瀀攀挀椀昀椀挀 渀攀甀琀爀愀氀椀稀椀渀最 antibodies showed that this effect of IL-18 was mediated by MR. The challenge with Pb18 also increased MR, TLR2 and਀吀䰀刀㐀 攀砀瀀爀攀猀猀椀漀渀⸀ 一漀 愀氀琀攀爀愀琀椀漀渀猀 漀渀 䠀㈀伀㈀ 氀攀瘀攀氀猀 眀攀爀攀 漀戀猀攀爀瘀攀搀⸀ 吀栀攀 挀栀愀氀氀攀渀最攀 眀椀琀栀 倀戀㄀㠀 愀渀搀 倀戀㈀㘀㔀 椀渀搀甀挀攀搀 洀漀渀漀挀礀琀攀猀 to produce IL-18, TNF-α, IL-10, IL-12 and IL-15. IL-18 production was associated with MR increase, while TNF-α and IL-਀㄀　 瀀爀漀搀甀挀琀椀漀渀 眀愀猀 愀猀猀漀挀椀愀琀攀搀 眀椀琀栀 吀䰀刀㐀 愀渀搀 吀䰀刀㈀ 爀攀猀瀀攀挀琀椀瘀攀氀礀⸀ 吀栀攀 栀椀最栀 䤀䰀ⴀ㄀㈀ 瀀爀漀搀甀挀琀椀漀渀 眀愀猀 渀漀琀 爀攀氀愀琀攀搀 眀椀琀栀 渀漀渀攀 漀昀 receptors studied. Conclusions: Our data indicate that, although IL-18 was able to induce high levels of proinflammatory cytokines which could act as resistance factors against P. brasiliensis, the effect of IL-18 on the increase of fungal recovery on monocytes would be due to modulation of MR, which in addition to facilitate the entry of the fungus in the cell, will activate a new molecular pathway that links engagement of the mannose receptor with peroxisome proliferator-activated਀爀攀挀攀瀀琀漀爀 ⠀倀倀䄀刀☀⌀㤀㐀㜀㬀⤀ 愀挀琀椀瘀愀琀椀漀渀Ⰰ 眀栀椀挀栀 爀攀最甀氀愀琀攀猀 琀栀攀 洀愀挀爀漀瀀栀愀最攀 椀渀昀氀愀洀洀愀琀漀爀礀 爀攀猀瀀漀渀猀攀Ⰰ 琀栀攀爀攀戀礀 瀀氀愀礀椀渀最 愀 爀漀氀攀 椀渀 瀀愀爀愀挀漀挀挀椀搀椀漀椀搀漀洀礀挀漀猀椀猀 瀀愀琀栀漀最攀渀攀猀椀猀⸀ 䘀椀渀愀渀挀椀愀氀 猀甀瀀瀀漀爀琀㨀 䘀䄀倀䔀匀倀 愀渀搀 䌀一倀焀⸀㰀⼀昀漀渀琀㸀㰀⼀瀀㸀㰀戀爀㸀㰀戀㸀䬀攀礀眀漀爀搀㨀 㰀⼀戀㸀☀渀戀猀瀀㬀栀甀洀愀渀 洀漀渀漀挀礀琀攀猀Ⰰ 䤀䰀ⴀ㄀㠀Ⰰ 洀愀渀渀漀猀攀 爀攀挀攀瀀琀漀爀Ⰰ 倀愀爀愀挀漀挀挀椀搀椀漀椀搀攀猀 戀爀愀猀椀氀椀攀渀猀椀猀Ⰰ 吀䰀刀猀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