Mannosyl-Recognizing Receptors Induce an M1-Like Phenotype in Macrophages of Susceptible Mice but an M2-Like Phenotype in Mice Resistant to a Fungal Infection

Autor(es)

Feriotti, Claudia ^[1] ; Loures, Flavio V. ^[1] ; de Araujo, Eliseu Frank ^[1] ; da Costa, Tania Alves ^[1] ; Calich, Vera L. G. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 8, n. 1 JAN 30 2013.
• Citações Web of Science: 24

Resumo

In addition to alpha1,3 glucan, mannan and mannan-linked proteins are expressed in the outer layer of Paracoccidioides brasiliensis yeasts. The recognition of mannosyl residues by multiple pathogen recognition receptors, such as the mannose receptor (MR), complement receptor 3 (CR3) and toll-like receptor 4 (TLR4) on macrophage membranes can influence macrophage activation and the mechanisms of innate immunity against fungal pathogens. The aim of this study was to clarify the role of these receptors in the interaction between P. brasiliensis and macrophages from resistant (A/J) and susceptible (B10,A) mice. Therefore, the phagocytic, fungicidal and secretory abilities of macrophages were evaluated in the presence of mannan and antibodies against MR, CR3 and TLR4. We verified that mannan increased and anti-MR antibody decreased the killing ability and nitric oxide production of macrophages. The specific blockade of MR, CR3 and TLR4 by monoclonal antibodies impaired fungal recognition and modulated the production of cytokines. Mannan or P. brasiliensis induced decreased expression of MR and TLR2 on A/J macrophages, whereas CR3, TLR4 and TLR2 were reduced on B10. A cells. Importantly, both mannan and P. brasiliensis induced the production of IL-12 by B10. A macrophages, whereas TGF-beta, TNF-alpha and IL-6 were produced by A/J cells. In addition, B10. A macrophages exhibited a prevalent expression of inducible NO-synthase and SOCS3 (suppressor of cytokine signaling-3), indicating a pro-inflammatory, ``M1-like{''} differentiation. In contrast, the elevated expression of arginase-1, found in inflammatory zone-1 (FIZZ1), YM1 (CHI313, chitinase-like lectin), and SOCS1, typical markers of alternatively activated macrophages, indicates a prevalent ``M2-like{''} differentiation of A/J macrophages. In conclusion, our data reveal that several mannosyl-recognizing receptors coordinate the apparently paradoxical innate response to paracoccidioidomycosis, in which resistance is initially mediated by alternatively activated phagocytes and tolerance to fungal growth, whereas susceptibility is linked to classically activated macrophages and the efficient control of fungal growth. (AU)

• Processo FAPESP: 05/55327-8 - Caracterização da função das células dendríticas na paracoccidioidomicose pulmonar murina e na determinação dos padrões de susceptibilidade e resistência ao fungo
• Beneficiário: Adriana Pina
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 04/14518-2 - Ativação do sistema imune na Paracoccidioidomicose pulmonar. Fatores do fungo e do hospedeiro que influenciam na gravidade da doença
• Beneficiário: Vera Lucia Garcia Calich
• Modalidade de apoio: Auxílio à Pesquisa - Temático