Characterization of pathogen receptors involved in the interaction between Paracoccidioides brasiliensis and macrophages from resistant and susceptible mice.

A paracoccidioidomicose é uma micose sistêmica da América Latina causada pelo fungo dimórfico Paraccoccidioides brasiliensis. Os TLRs, e os CLRs são \"Receptores de Reconhecimento Padrão\" (PRRs) que reconhecem os \"Padrões Moleculares Associados aos Patógenos\" (PAMPs). O objetivo deste trabalho foi caracterizar os receptores de macrófagos de camundongos resistentes (A/J) e susceptíveis (B10.A) ao P. brasiliensis envolvidos na interação com o fungo, através do estudo do efeito do tratamento dos macrófagos com agonistas ou antagonistas dos receptores de manose (MR), receptores do tipo Toll 4 (TLR4), receptores de beta-glucanas (dectina-1) e receptores de complemento CR3 (CD11b/CD18), na interação fungo-macrófago. O tratamento dos macrófagos com o agonista de MR (manana), ativou ambos os macrófagos A/J e B10.A. O bloqueio dos receptores MR, TLR4 e CR3 com anticorpos monoclonais específicos, induziu inibição dos macrófagos, mostrando a importância destes receptores no reconhecimento dos carboidratos presentes na parede do fungo. O tratamento com os agonistas de dectina-1 (laminarina e curdlan) induziram ativação dos macrófagos, porém de maneira distinta entre as linhagens. A laminarina pareceu ativar macrófagos B10.A e inibir A/J; curdlan por sua vez, pareceu ativar macrófagos A/J e inibir B10.A.Estes dados sugerem que diferentes perfis de ativação dos macrófagos atuem no reconhecimento do fungo.Paracoccidioidomycosis is a systemic mycosis of Latin America caused by Paraccoccidioides brasiliensis, a dimorphic fungus. The TLRs and CLRs are \"Pattern Recognition Receptors\" (PRRs) which recognize \"Pathogen Associated Molecular Patterns\" (PAMPs). The aim of our work was to characterize the macrophages receptors from resistant (A/J) and susceptible (B10.A) mice to P. brasiliensis involved in the interaction with the fungus. We studied the effect of macrophages treatment with agonists or antagonists of mannose receptors (MR), Toll like receptors 4 (TLR4), b-glucans receptors (dectin-1) and complement receptors CR3 (CD11b/CD18), in the interaction fungus-macrophages. The macrophages treatment with mannan agonist of MR activated both A/J and B10.A macrophages. The blockade of MR, TLR4 and CR3 receptors with specific monoclonal antibodies, induced macrophages inhibition, showing the importance of these receptors in the recognition of common carbohydrates presents on the cell wall of the fungus. The macrophages treatment with laminarin and curdlan agonists of dectin-1, induced macrophages activation, however in the distinct manner between both macrophages lineages. Laminarin appeared to activate B10.A macrophages and inhibit A/J; whereas curdlan appeared to activate A/J macrophages and inhibit B10.A. These data suggest that a different profile of macrophages activation plays in the fungus recognition