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ArtinM offers new perspectives in the development of antifungal therapy.

Ruas LP, Carvalho FC, Roque-Barreira MC - Front Microbiol (2012)

Bottom Line: Despite significant developments in antifungal chemotherapy, its efficacy remains limited since drug therapy is prolonged and associated with toxic side effects and relapses.A carbohydrate recognition-based interaction of ArtinM with Toll-like receptor 2 (TLR2) accounts for initiating the immunomodulatory effect of the lectin.The precise identification of the TLR2 N-glycan(s) targeted by ArtinM may support novel basis for the development of antifungal therapy.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.

ABSTRACT
The thermally dimorphic fungus Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis (PCM), the most frequent systemic mycosis that affects the rural populations in Latin America. Despite significant developments in antifungal chemotherapy, its efficacy remains limited since drug therapy is prolonged and associated with toxic side effects and relapses. In response to these challenges, it is now recognized that several aspects of antifungal immunity can be modulated to better deal with fungal infections. A common idea for halting fungal infections has been the need to activate a cell-based, pro-inflammatory Th1 immune response to improve the fungal elimination. ArtinM, a D-mannose binding lectin from Artocarpus heterophyllus, has the property of modulating immunity against several intracellular pathogens. Here, we review the immunomodulatory activity of ArtinM during experimental PCM in mice. Both prophylactic and therapeutic protocols of ArtinM administration promotes a Th1 immune response balanced by IL-10, which outstandingly reduces the fungal load in organs of the treated mice while maintaining a controlled inflammation at the site of infection. A carbohydrate recognition-based interaction of ArtinM with Toll-like receptor 2 (TLR2) accounts for initiating the immunomodulatory effect of the lectin. The precise identification of the TLR2 N-glycan(s) targeted by ArtinM may support novel basis for the development of antifungal therapy.

No MeSH data available.


Related in: MedlinePlus

ArtinM administration prevents pulmonary lesions in P.brasiliensis-infected mice. Lung histopathology of uninfected mice (A), P.brasiliensis-infected mice (B), and P. brasiliensis-infected mice treated with ArtinM (C). P. brasiliensis-infected mice display extensive and confluent lesions in the lungs, with epithelioid granulomas surrounding a large number of yeast cells. Infected mice treated with ArtinM present no granulomas, and lung architecture is similar to that of uninfected mice. The lung sections were stained with H&E (Modified from Coltri et al., 2010)
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Figure 1: ArtinM administration prevents pulmonary lesions in P.brasiliensis-infected mice. Lung histopathology of uninfected mice (A), P.brasiliensis-infected mice (B), and P. brasiliensis-infected mice treated with ArtinM (C). P. brasiliensis-infected mice display extensive and confluent lesions in the lungs, with epithelioid granulomas surrounding a large number of yeast cells. Infected mice treated with ArtinM present no granulomas, and lung architecture is similar to that of uninfected mice. The lung sections were stained with H&E (Modified from Coltri et al., 2010)

Mentions: Knowledge about the immunomodulatory effects of ArtinM on PCM is derived from studies that used an experimental model developed in BALB/c mice that had been intravenously infected with P. brasiliensis. Trials involving several protocols for the therapeutic and prophylactic administration of ArtinM showed that the most effective therapeutic protocol consisted of a single subcutaneous injection of ArtinM 10 days after infection, whereas the best prophylaxis was attained by the administration of two subcutaneous injections of ArtinM on day 10 and day 3 before infection. The beneficial effects of therapeutic and prophylactic regimens (Coltri et al., 2008, 2010) of ArtinM on the severity of P. brasiliensis infection, which manifested on day 30 post-infection, included marked decrease in fungal burden and absence of granulomas in the lungs, which exhibited a well-preserved bronchoalveolar architecture. This pattern was in contrast to what was observed in the untreated mice, which had disseminated infection and multiple sites of focal and confluent epithelioid granulomas with lymphomonocytic halos circumscribing a high number of viable and non-viable yeast cells (Figure 1). The lesions were larger and still disseminated on day 60 after infection, while ArtinM-treated mice had no granulomas or yeast cells in the liver, spleen or lung tissue.


ArtinM offers new perspectives in the development of antifungal therapy.

Ruas LP, Carvalho FC, Roque-Barreira MC - Front Microbiol (2012)

ArtinM administration prevents pulmonary lesions in P.brasiliensis-infected mice. Lung histopathology of uninfected mice (A), P.brasiliensis-infected mice (B), and P. brasiliensis-infected mice treated with ArtinM (C). P. brasiliensis-infected mice display extensive and confluent lesions in the lungs, with epithelioid granulomas surrounding a large number of yeast cells. Infected mice treated with ArtinM present no granulomas, and lung architecture is similar to that of uninfected mice. The lung sections were stained with H&E (Modified from Coltri et al., 2010)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3375580&req=5

Figure 1: ArtinM administration prevents pulmonary lesions in P.brasiliensis-infected mice. Lung histopathology of uninfected mice (A), P.brasiliensis-infected mice (B), and P. brasiliensis-infected mice treated with ArtinM (C). P. brasiliensis-infected mice display extensive and confluent lesions in the lungs, with epithelioid granulomas surrounding a large number of yeast cells. Infected mice treated with ArtinM present no granulomas, and lung architecture is similar to that of uninfected mice. The lung sections were stained with H&E (Modified from Coltri et al., 2010)
Mentions: Knowledge about the immunomodulatory effects of ArtinM on PCM is derived from studies that used an experimental model developed in BALB/c mice that had been intravenously infected with P. brasiliensis. Trials involving several protocols for the therapeutic and prophylactic administration of ArtinM showed that the most effective therapeutic protocol consisted of a single subcutaneous injection of ArtinM 10 days after infection, whereas the best prophylaxis was attained by the administration of two subcutaneous injections of ArtinM on day 10 and day 3 before infection. The beneficial effects of therapeutic and prophylactic regimens (Coltri et al., 2008, 2010) of ArtinM on the severity of P. brasiliensis infection, which manifested on day 30 post-infection, included marked decrease in fungal burden and absence of granulomas in the lungs, which exhibited a well-preserved bronchoalveolar architecture. This pattern was in contrast to what was observed in the untreated mice, which had disseminated infection and multiple sites of focal and confluent epithelioid granulomas with lymphomonocytic halos circumscribing a high number of viable and non-viable yeast cells (Figure 1). The lesions were larger and still disseminated on day 60 after infection, while ArtinM-treated mice had no granulomas or yeast cells in the liver, spleen or lung tissue.

Bottom Line: Despite significant developments in antifungal chemotherapy, its efficacy remains limited since drug therapy is prolonged and associated with toxic side effects and relapses.A carbohydrate recognition-based interaction of ArtinM with Toll-like receptor 2 (TLR2) accounts for initiating the immunomodulatory effect of the lectin.The precise identification of the TLR2 N-glycan(s) targeted by ArtinM may support novel basis for the development of antifungal therapy.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.

ABSTRACT
The thermally dimorphic fungus Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis (PCM), the most frequent systemic mycosis that affects the rural populations in Latin America. Despite significant developments in antifungal chemotherapy, its efficacy remains limited since drug therapy is prolonged and associated with toxic side effects and relapses. In response to these challenges, it is now recognized that several aspects of antifungal immunity can be modulated to better deal with fungal infections. A common idea for halting fungal infections has been the need to activate a cell-based, pro-inflammatory Th1 immune response to improve the fungal elimination. ArtinM, a D-mannose binding lectin from Artocarpus heterophyllus, has the property of modulating immunity against several intracellular pathogens. Here, we review the immunomodulatory activity of ArtinM during experimental PCM in mice. Both prophylactic and therapeutic protocols of ArtinM administration promotes a Th1 immune response balanced by IL-10, which outstandingly reduces the fungal load in organs of the treated mice while maintaining a controlled inflammation at the site of infection. A carbohydrate recognition-based interaction of ArtinM with Toll-like receptor 2 (TLR2) accounts for initiating the immunomodulatory effect of the lectin. The precise identification of the TLR2 N-glycan(s) targeted by ArtinM may support novel basis for the development of antifungal therapy.

No MeSH data available.


Related in: MedlinePlus