title: MyD88 Adapter-like (Mal)/TIRAP Is Required for Cytokine Production by Splenic Ly6CloTLR2hi but Not by Ly6ChiTLR2hi Monocytes during Trypanosoma cruzi Infection.
abstract: This study continues to explore the plasticity of Toll-like receptor 2 (TLR2) previously described in immune response during Trypanosoma cruzi infection. Here, we have shown that Ly6ChiTLR2himonocytes were involved in TNF-α and IL-12 production, whereas Ly6CloTLR2himonocytes were mainly committed to IL-10 and TNF-α production during T. cruzi infection independently of TLR agonist used (i.e. TLR2 or TLR9 agonists). Another difference between the monocyte populations is that the adapter Mal (encoded by TIRAP) has appeared crucial for the cytokine production by Ly6Clobut not by Ly6Chimonocytes. The protein Mal was necessary to induce cytokine synthesis by Ly6Clomonocytes after triggering TLR2 or TLR9. Finally, our data have suggested that TLR2, TLR9, and Mal/TIRAP controlled differentially the emergence of the different TLR2himonocyte populations in the spleen. In summary, this study highlights the central role of the TLR2/Mal tandem in the distinct activity among the monocyte subsets during T. cruzi infection. Such findings provide a basis for understanding the challenge posed by the use of TLR2 agonist in immunotherapy.
authors.affiliation: From the Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, 31270-910 Belo Horizonte, Minas Gerais, Brazil and.
authors.forename: Humberto Doriguêtto
authors.initials: HD
authors.lastname: Gravina
authors.affiliation: From the Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, 31270-910 Belo Horizonte, Minas Gerais, Brazil and.
authors.forename: Alfredo Miranda
authors.initials: AM
authors.lastname: Goes
authors.affiliation: Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, 30190-002 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Silvane Maria Fonseca
authors.initials: SM
authors.lastname: Murta
authors.affiliation: From the Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, 31270-910 Belo Horizonte, Minas Gerais, Brazil and ropertcatherine@gmail.com.
authors.forename: Catherine
authors.initials: C
authors.lastname: Ropert
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000276:immunology*; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology; D016207:Cytokines / Q000276:immunology*; D007113:Immunity, Innate; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology* / Q000469:parasitology; D017472:Receptors, Interleukin-1 / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000469:parasitology; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D000950:Antigens, Ly; D016207:Cytokines; C494192:Ly-6C antigen, mouse; D008562:Membrane Glycoproteins; D017472:Receptors, Interleukin-1; C499045:TIRAP protein, mouse; C493486:Tlr2 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051217:Toll-Like Receptor 9
keywords: MAL/TIRAP; Toll-like receptor (TLR); cytokine; flow cytometry; infection; inflammation; innate immunity; monocyte