XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:170-3

Poster (Painel)

170-3

INFLUENCE OF FUNGAL VIRULENCE ON CYTOKINES EXPRESSION IN GRANULOMATOUS LESIONS OF P. BRASILIENSIS-INOCULATED INBRED MICE

Authors:

Liana Verinaud (UNICAMP - Universidade Estadual de Campinas) ; Angela Satie Nishikaku (USP - Universidade de Sao PauloUNIFESP - Universidade Federal de Sao Paulo) ; Jose Vicente Alves (USP - Universidade de Sao Paulo) ; Raphael Fagnani Sanchez 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) ; Eva Burger (USP - Universidade de Sao Paulo)

Abstract

Paracoccidioidomycosis is the most prevalent systemic mycosis in Latin America. Of the many clinical manifestations of the disease, severe and mild forms may be determined by the genetic background of the patients; however the importance of variations in fungal virulence cannot be excluded. Indeed, in previous works we showed that 120 days after infection with a highly virulent Paracocidioides brasiliensis isolate susceptible (S) mice develop loose disseminated granulomas and resistant (R) mice show compact circumscribed granulomas. On the other hand, infection with an isolate of low virulence, initially elicits formation of active granulomas, which at later stages become residual.਀䠀攀爀攀眀攀愀渀愀氀礀猀攀琀栀攀瀀愀爀琀椀挀椀瀀愀琀椀漀渀漀昀挀礀琀漀欀椀渀攀猀椀渀琀栀攀搀攀瘀攀氀漀瀀洀攀渀琀漀昀最爀愀渀甀氀漀洀愀猀漀昀匀愀渀搀刀洀椀挀攀椀瀀椀渀昀攀挀琀攀搀眀椀琀栀琀栀攀猀氀椀最栀琀氀礀瘀椀爀甀氀攀渀琀倀戀㈀㘀㔀Ⰰ 椀渀挀漀洀瀀愀爀椀猀漀渀眀椀琀栀琀栀攀最爀愀渀甀氀漀洀愀猀愀爀挀栀椀琀攀挀琀甀爀攀Ⰰ 琀栀攀愀爀攀愀猀漀昀氀攀猀椀漀渀猀挀漀洀瀀爀椀猀椀渀最倀戀眀椀琀栀瀀爀攀猀攀爀瘀攀搀漀爀愀氀琀攀爀攀搀洀漀爀瀀栀漀氀漀最礀愀渀搀琀栀攀瀀爀攀猀攀渀挀攀愀渀搀搀椀猀琀爀椀戀甀琀椀漀渀漀昀搀椀昀昀攀爀攀渀琀挀攀氀氀瀀漀瀀甀氀愀琀椀漀渀猀⸀ Infection with Pb265 initially developed loose lesions that tended to resolution, as indicated by the reduction of the lesion area and the percentage of the area occupied by Pb, confirming the regressive nature of this infection even in S mice and confirming the role of fungal virulence in the development of different outcomes of Pb infection.਀䤀渀戀漀琀栀洀漀甀猀攀猀琀爀愀椀渀猀Ⰰ 猀攀挀爀攀琀椀漀渀漀昀琀栀攀猀琀甀搀椀攀搀挀礀琀漀欀椀渀攀猀眀愀猀昀漀甀渀搀氀漀挀愀氀氀礀愀琀㄀㔀搀愀礀猀愀昀琀攀爀椀渀昀攀挀琀椀漀渀Ⰰ 戀甀琀愀琀㄀㈀　搀愀礀猀Ⰰ 瘀攀爀礀昀攀眀挀攀氀氀猀瀀漀猀椀琀椀瘀攀琀漀吀一䘀ⴀ☀⌀㘀㄀㔀㌀㜀㬀愀渀搀䤀䘀一ⴀ☀⌀㘀㄀㔀㐀㌀㬀爀攀洀愀椀渀攀搀Ⰰ 眀栀攀爀攀愀猀猀漀洀攀猀琀椀氀氀瀀爀漀搀甀挀攀搀吀䜀䘀ⴀ☀⌀㘀㄀㔀㌀㠀㬀⸀ 吀栀椀猀瀀栀攀渀漀洀攀渀漀渀洀愀礀攀瘀攀渀琀甀愀氀氀礀戀攀攀砀瀀氀愀椀渀攀搀戀礀琀栀攀椀爀爀攀氀攀瘀愀渀挀攀漀昀猀琀椀洀甀氀愀琀漀爀礀挀礀琀漀欀椀渀攀猀愀琀琀栀攀猀椀琀攀漀昀愀爀攀猀椀搀甀愀氀椀渀昀攀挀琀椀漀渀Ⰰ 戀甀琀琀栀攀渀攀挀攀猀猀椀琀礀漀昀爀攀最甀氀愀琀漀爀礀挀礀琀漀欀椀渀攀猀琀漀攀爀愀搀椀挀愀琀攀琀栀攀椀渀昀氀愀洀洀愀琀漀爀礀爀攀猀瀀漀渀猀攀⸀ We studied the expression of mRaNAs and the in situ presence of IFN-γ, TNF-α, TGF-β and IL-10 in granulomas in the omentum of these mice at 120 days, when the infection was under control in both mouse strains. RT-PCR revealed much higher expression of all studied cytokines in R than in S animals (8, 35, 30 and 20 folds respectively for IFN-γ, TNF-α, TGF-β and IL-10). This finding suggests that although both, R and S animals are able to efficiently control low virulence Pb infection, the mRNAs synthesis of these cytokines is maintained for a longer time-span in the R strain. However, the mRNAs expression was not in parallel with the protein synthesis of these cytokines: immunohistochemistry revealed an extremely low percentage of low intensity positive cells in the granulomas of either S or R animals. This fact suggests that although the mRNAs is still being secreted as the infection is restrained (at a higher level in R mice), there is a further control on the protein synthesis in both mouse strains.਀ ਀匀唀倀倀伀刀吀㨀䘀䄀倀䔀匀倀 ⌀ 　㘀⼀㘀　　㤀㄀ⴀ㘀 ☀ ⌀ 　㠀⼀㔀㠀㘀　㐀ⴀ　㬀䌀一倀焀㌀　㐀㘀㌀　⼀㈀　　㤀ⴀ㠀

Keyword: Fungal strains, virulence, Granulomatous lesions, cytokines

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