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.
Highlights
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
IL-12 production by ArtinM-stimulated macrophages was inhibited by D-mannose, which indicates that its production is dependent on the lectin carbohydrate-recognition domain (CRD). These results demonstrate that Toll-like receptor 2 (TLR2) plays a critical role in ArtinM-mediated production of IL-12 (Coltri et al, 2008)
CONCLUDING REMARKS AND PERSPECTIVES ArtinM administration interferes with the outcome of P. brasiliensis infection by modulating host immunity according to the following events: (a) recognition of TLR2 glycans by the lectin, (b) induction of IL-12 production, (c) generation of Th1-balanced immunity, and (d) protection against P. brasiliensis, mainly manifested by the occurrence of milder lung lesions and low fungal burden
Summary
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. We discuss the role of a plant lectin named ArtinM in a murine model of Paracoccidioides brasiliensis infection, highlighting its immunomodulatory properties and the importance of the modulation of a cell-mediated immune response in the resistance to the fungus.
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