Abstract

Introduction: The chronic adult form of Paracoccidioidomycosis (PCM) may take months to years to fully develop; consequently, when the patients are finally diagnosed, pulmonary lesions are already well established exhibiting different developmental stages. Our aim was to define the various stages occurring during the course of the experimental pulmonary PCM. ਀㰀戀㸀䴀攀琀栀漀搀漀氀漀最礀㨀㰀⼀戀㸀 䈀䄀䰀䈀⼀挀 洀椀挀攀 眀攀爀攀 椀渀漀挀甀氀愀琀攀搀 椀渀琀爀愀渀愀猀愀氀氀礀 眀椀琀栀 倀戀ⴀ挀漀渀椀搀椀愀 ⠀渀㴀㔀　⤀ 漀爀 倀䈀匀 ⠀渀㴀㔀　⤀⸀ 䰀甀渀最猀 眀攀爀攀 猀琀甀搀椀攀搀 愀昀琀攀爀 ㈀ⴀ栀漀甀爀猀Ⰰ 㐀Ⰰ 㠀Ⰰ ㄀㈀ 愀渀搀 ㄀㘀ⴀ眀欀猀 瀀漀猀琀ⴀ椀渀昀攀挀琀椀漀渀 ⠀瀀⸀椀⤀⸀ 倀甀氀洀漀渀愀爀礀 椀渀昀氀愀洀洀愀琀椀漀渀Ⰰ 昀甀渀最椀 愀渀搀 挀漀氀氀愀最攀渀 眀攀爀攀 焀甀愀渀琀椀昀椀攀搀 戀礀 搀椀最椀琀愀氀 栀椀猀琀漀瀀愀琀栀漀氀漀最礀⼀栀椀猀琀漀洀漀爀瀀栀漀洀攀琀爀礀⸀ 䄀搀搀椀琀椀漀渀愀氀氀礀Ⰰ 愀 ㌀㄀ⴀ挀礀琀漀欀椀渀攀 戀椀漀瀀氀攀砀 愀猀猀愀礀 眀愀猀 甀猀攀搀 琀漀 搀攀昀椀渀攀 挀礀琀漀欀椀渀攀 瀀爀漀昀椀氀攀猀⸀  Results: The following chronologic stages were defined: Stage one (2-hours p.i): mild septal infiltration composed by neutrophils and macrophages accompanied by an intense “cytokine burst” represented by significant increases in IL-1α,IL-1β,IL-4,IL-5,IL-6,IL-10,IL12p70,IL-13,IL-17,Eotaxin,G-CSF,MCP1,MIP1α,MIP1β,GM-CSF,IFN-γ and TNF-α levels. Stage two (4-wks p.i): presence of nodules, evidence of incipient periarterial- and intense but disperse parenchymal-inflammation accompanied by hyper-secretion of those cytokines and chemokines mentioned in the first stage of infection. Stages third and fourth (8 and 12-wks p.i): fungal proliferation, inflammation and collagenesis reached their highest intensity with particular involvement of the periarterial space. Paradoxically, lung cytokines and chemokines were down-regulated with significant decreases in IL-2,IL-3,IL-5,IL-9,IL-13,IL-15,GM-CSF,IFN-γ,MIP1β and TNF-α. Stage fifth (16-wks p.i): inflammation decreased becoming limited to pseudotumoral masses and was accompanied by a “silent” cytokine response, except for PDGF,MIG,RANTES and IL12p40 which remained up-regulated for the duration of the experiment. ਀㰀戀㸀䌀漀渀挀氀甀猀椀漀渀㨀㰀⼀戀㸀 䤀渀昀氀愀洀洀愀琀漀爀礀 爀攀愀挀琀椀漀渀 眀愀猀 搀礀渀愀洀椀挀 眀椀琀栀 氀攀猀椀漀渀猀 琀栀愀琀 眀攀渀琀 昀爀漀洀 搀椀猀瀀攀爀猀攀 瀀愀爀攀渀挀栀礀洀愀氀 椀渀昀氀愀洀洀愀琀椀漀渀Ⰰ 眀攀氀氀 搀攀昀椀渀攀搀 渀漀搀甀氀攀猀Ⰰ 瀀攀爀椀愀爀琀攀爀椀愀氀 猀栀攀愀琀栀 椀渀昀氀愀洀洀愀琀椀漀渀 琀漀 瀀猀攀甀搀漀琀甀洀漀爀愀氀 洀愀猀猀攀猀⸀ 䌀礀琀漀欀椀渀攀 瀀爀漀昀椀氀攀猀 愀氀猀漀 挀栀愀渀最攀搀 愀挀挀漀爀搀椀渀最 琀漀 琀椀洀攀 瀀⸀椀 眀椀琀栀 瀀爀漀ⴀ椀渀昀氀愀洀洀愀琀漀爀礀 挀礀琀漀欀椀渀攀猀 戀甀爀猀琀 愀琀 攀愀爀氀礀 眀攀攀欀猀 瀀⸀椀 琀栀愀琀 猀甀戀猀椀搀攀搀 氀愀琀攀爀 漀渀 琀漀 爀攀愀挀栀 椀洀洀甀渀漀猀甀瀀瀀爀攀猀猀椀瘀攀 挀漀渀搀椀琀椀漀渀猀 愀琀 氀愀琀攀爀 猀琀愀最攀猀⸀   Financial support: COLCIENCIAS grants No 2213-408-20412 and 2213-04-16439. ਀䄀甀琀栀漀爀猀 ㄀ 愀渀搀 ㈀ 挀漀渀琀爀椀戀甀琀攀搀 攀焀甀愀氀氀礀 琀漀 琀栀椀猀 眀漀爀欀⸀ 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☀渀戀猀瀀㬀䤀洀洀甀渀漀栀椀猀琀漀瀀愀琀栀漀氀漀最礀Ⰰ 䌀礀琀漀欀椀渀攀 瀀爀漀昀椀氀攀猀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