title: Interactions between TLR2, TLR4, and mannose receptors with gp43 from Paracoccidioides brasiliensis induce cytokine production by human monocytes.
abstract: The glycoprotein gp43 is an immunodominant antigen secreted by Paracoccidioides brasiliensis, the agent of paracoccidioidomycosis. The present study evaluated whether gp43 can interact with toll-like (TLR2, TLR4) and mannose (MR) receptors on the surface of human monocytes, and how that affects their expression and cytokine production. Monocytes were incubated with or without monoclonal antibodies anti-TLR2, anti-TLR4, or anti-MR, individually or in combination, prior to the addition of gp43. The gp43 binding to monocyte surface, as well as expression of TLR2, TLR4, and MRs were analyzed by flow cytometry, while production of TNF-α and IL-10 was monitored by ELISA. The results suggested that gp43 binds to TLR2, TLR4, and MR receptors, with TLR2 and MR having the strongest effect. All three receptors influenced the production of IL-10, while TNF-α production was associated with expression of TLR4 and MR. The modulatory effect of gp43 was demonstrated by high levels of TLR4 expression associated with increased production of TNF-α after 4 h of culture. Alternatively, high levels of TLR2 expression, and elevated production of IL-10, were detected after 18 h. We showed that interaction between gp43 and monocytes may affect the innate immune response by modulating the expression of the pattern recognition receptors TLR2, TLR4 and MR, as well as production of pro- and anti-inflammatory cytokines.
authors.affiliation: Departamento de Microbiologia e Imunologia, Instituto de Biociências, Universidade Estadual Paulista, UNESP, Botucatu, São Paulo, Brazil.
authors.forename: Erika
authors.initials: E
authors.lastname: Nakaira-Takahagi
authors.forename: Marjorie A
authors.initials: MA
authors.lastname: Golim
authors.forename: Camila F
authors.initials: CF
authors.lastname: Bannwart
authors.forename: Rosana
authors.initials: R
authors.lastname: Puccia
authors.forename: Maria T S
authors.initials: MT
authors.lastname: Peraçoli
mesh_terms: D000328:Adult; D000946:Antigens, Fungal / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000276:immunology / Q000378:metabolism*; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D010228:Paracoccidioides / Q000276:immunology; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: C103180:43 kDa protein, Paracoccidioides; D000946:Antigens, Fungal; D005656:Fungal Proteins; D006023:Glycoproteins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10