Sporotrichosis is often manifested as a chronic granulomatous infection and the monocytes/macrophages play a central role in the host defense system. Surface components of Sporothrix schenckii have been characterized and suggestions have been made as to their possible role in pathogenicity. Ergosterol peroxide, cell-wall compounds (alkali-insoluble fraction-F1 and lipid extract-LEY), and exoantigen from the yeast form of the fungus have been characterized as virulence factors, activating both innate, by cytotoxins linked to the activation of reactive oxygen and nitrogen species (H2O2 and NO), and adaptive immune response to produce cytokines Th1 and Th2 profile. In this study, preliminary results have demonstrated that, in systemic sporotrichosis, TLR-4 triggers the innate immune response, activating an oxidative burst. These data represent the first report of the participation of TLR-4 in murine sporotrichosis, in the presence of lipids from the cell wall of S. schenckii. These results taken together may open new perspectives of study leading to an antifungal agent that could be used to benefit the entire population.

No abstract

In an attempt to elucidate the effects of Sporothrix schenckii infection on the immune response, our laboratory has developed a murine model of disseminated sporotrichosis. Helper T cells can be further subdivided into Th1 and Th2 phenotypes. The differentiation of two subsets of T lymphocytes is driven by IL-12 and IL-4 cytokines, respectively. Th1 cells produce IFN-gamma that activate macrophages and promote cell-mediated immunity. In addition, we found low levels of iNOS and NO production in the initial (1st and 2nd weeks) and final (9th and 10th weeks) periods of the infection, in contrast with the period of week 4 to 7 of elevated values. The determination of IFN-gamma and IL-12 are in agreement with NO/iNOS detection, showing the presence of cellular immune response throughout the infectious process. However, the production of IL-4 shows an increase in levels after the 5th and 6th weeks suggesting a participation of Th2 response in this period as well. Regarding these results, the study demonstrated that in experimental sporotrichosis infection the cellular immune response participated throughout the period analyzed as a nitric oxide dependent mechanism. In contrast, the presence of Th2 response began in the 5th week, suggesting the participation of humoral immune response in advanced stages of sporotrichosis.

No abstract

Sporotrichosis is an infection caused by the dimorphic fungus Sporothrix schenckii. Toll-like receptors (TLRs) play an important role in immunity, since they bind to pathogen surface antigens and initiate the immune response. However, little is known about the role of TLR-2 and fungal surface antigens in the recognition of S. schenckii and in the subsequent immune response. This study aimed to evaluate the involvement of TLR-2 and fungal surface soluble (SolAg) and lipidic (LipAg) antigens in phagocytosis of S. schenckii and production of immune mediators by macrophages obtained from WT and TLR-2(-/-) animals. The results showed that TLR-2(-/-) animals had had statistical lower percentage of macrophages with internalized yeasts compared to WT. SolAg and LipAg impaired phagocytosis and immunological mediator production for both WT and TLR-2(-/-). The absence of TLR-2 led to lower production of the cytokines TNF-α, IL-1β, IL-12 and IL-10 compared to WT animals. These results suggest a new insight in relation to how the immune system, through TLR-2, recognizes and induces the production of mediators in response to the fungus S. schenckii.

Supporting information FTIR data (KBr, cm -1 ) [Eu(TTA) 3 (Bpy-Si)]: 3 431 υ as (NH); 3 090 υ as (CH); 1 627 υ s (C=O); 1 578, 1 520, 1 υ(C=C, C=S); 1 357 υ as (C-F); 682 δ(C-F); 456 υ(Eu-(Bpy-Si)); 1 578 υ(C=C, C=N ring), 1 υ(Si-C); 1 089 υ(Si-O-C); 962 δ(Si-O) and 790 δ(CH ar ). [Ga(TTA) 3 (Bpy-Si)] 3 410 υas(NH); 3 090 υ as (CH); 1 654 υ s (C=O); 1 578, 1 520, 1 υ(C=C, C=S); 1 358 υ as (C-Cl); 680 δ(C-Cl); 456 υ(Gd-L). DRIFT SiO 2 -[Eu(TTA) 3 (Bpy-Si)] and SiO 2meso -[Eu(TTA) 3 (Bpy-Si)]: 2980 ν as (CH 2 ,CH 3 ); 2 ν s (CH 2 ,CH 3 ), 1 629 υ(C=O); 1414 υ(C=C, C=S); 1238-1050 υ(Si-C) , υ(Si-O),υ(Si-O-C); δ(Si-O-Si) and 796 δ(Si-O-C). SiO 2 @[Eu(TTA) 3 (Bpy-Si)]: 2 980 ν as (CH 2 ,CH 3 ); 2 878 ν s (CH 2 ,CH 3 ), 1 640 υ(C=O); 1 υ(C=C + C=S); 1 230-1 050 υ(Si-C), υ(Si-O), υ(Si-O-C); 950 δ(Si-O-Si) and 800 δ(Si-O-C).

The response of hydrogen peroxide (H 2 O 2) and cytokines during an experimental sporotrichosis in male Swiss mice was assessed over a period of 10 weeks by monitoring macrophage activation challenged with exoantigen (ExoAg) from the fungus Sporothrix schenckii. The studied endpoints were: H 2 O 2 production, fungal burden at spleen, apoptosis in peritoneal macrophages, and IL-1b, IL-6, IL-2, IL-10 production. During the two first weeks of infection was observed low burden of yeast in spleen and high response of H 2 O 2 , IL-2, and IL-1b. The weeks of highest fungal burden (fourth-sixth) coincided with major apoptosis in peritoneal macrophages, normal production of IL-6 and lower production of H 2 O 2 , IL-2, and IL-1b, suggesting a role for these three last in the early control of infection. On the other hand, IL-1b (but not IL-6) was recovered since the sixth week, suggesting a possible role in the late phase of infection, contributing to the fungal clearance in conjunction with the specific mechanisms. The IL-10 was elevated until the sixth, principally in the second week. These results evidences that ExoAg is involved in the host immune modulation, influencing the S. Schenckii virulence, and its role is related with the time of the infection in the model used.

Sporotrichosis is a subcutaneous mycosis that is caused by the dimorphic fungus Sporothrix schenckii. This disease generally occurs within the skin and subcutaneous tissues, causing lesions that can spread through adjacent lymphatic vessels and sometimes leading to systemic diseases in immunocompromised patients. Macrophages are crucial for proper immune responses against a variety of pathogens. Furthermore, macrophages can play different roles in response to different microorganisms and forms of activation, and they can be divided into "classic" or "alternatively" activated populations, as also known as M1 and M2 macrophages. M1 cells can lead to tissue injury and contribute to pathogenesis, whereas M2 cells promote angiogenesis, tissue remodeling, and repair. The aim of this study was to investigate the roles of M1 and M2 macrophages in a sporotrichosis model. Toward this end, we performed phenotyping of peritoneal exudate cells and evaluated the concomitant production of several immunomediators, including IL-12, IL-10, TGF-β, nitric oxide, and arginase-I activity, which were stimulated ex vivo with cell wall peptide-polysaccharide. Our results showed the predominance of the M2 macrophage population, indicated by peaks of arginase-I activity as well as IL-10 and TGF-β production during the 6th and 8th weeks after infection. These results were consistent with cellular phenotyping that revealed increases in CD206-positive cells over this period. This is the first report of the participation of M2 macrophages in sporotrichosis infections.