XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:11-1

Investigação

11-1	The role of IL-18 in Paracoccidioides brasiliensis antifungal activities of human monocytes
Authors:	Luciane Alarcão Dias-melicio (UNESP- IB - Universidade Estadual Paulista) ; Angela Maria Victoriano de Campos Soares (UNESP- IB - Universidade Estadual Paulista)

Abstract

In recent years, our group has evaluated the mechanisms involved in the interaction of P. brasiliensis with human phagocytic cells that results in fungus killing. Interleukin -18 ( IL-18) is a cytokine that contributes to host defense infection by increasing antimicrobial function of phagocytes and initiating TH1 and TH17 adaptative immune responses. The role of this cytokine in paracoccidioidomycosis is not fully understood, and to date there are no studies on its role in antifungal activities of phagocytic cells. In this context, we assessed the action of IL-18 on human monocytes activities against P. brasiliensis by evaluating fungicidal activity and H2O2 release. In addition, we studied IL-18 capacity to modulate TLR2, TLR4 and mannose receptor (MR) expression, as well as IL-18, IL-10, TNF-alfa, IL-12 and IL-15 production by these cells. Unexpectedly, the results showed that IL-18 increased fungal recovery from infected monocytes. Accordingly, H2O2, a metabolite involved in P.brasiliensis killing, was not affected. In addition, IL-18 increases MR and TLR4 expression and TNF-alfa and IL-10 production by monocytes. Blocking assays revealed that IL-18 role in P. brasiliensis growth in human monocytes is mediated by MR, while increase in TNF-alfa and IL-10 levels was associated with TLR4 and TLR2 respectively. Our data strongly suggest that, although IL-18 was able to induce high levels of pro and anti-inflammatory cytokines, which potentially could act as modulators of phagocytic cells activity, the effect of IL-18 on the increase of fungal recovery on monocytes, would be due to capacity of this cytokine to modulate MR expression. We are hypothesizing that increase on MR expression in monocytes, by IL-18, will both, facilitate the entry of the fungus in the cell, and activate a new molecular pathway involving peroxisome proliferator-activated receptor (PPAR&gamma)activation, which regulates the macrophage inflammatory response, thereby playing a role in paracoccidioidomycosis pathogenesis. ਀ ਀䘀椀渀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

Keyword: antifungal activity, IL-18, mannose receptor, monocytes, Paracoccidioides brasiliensis

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