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

• DOI: 10.1371/journal.pone.0054845
• Publication Date: 2013-01-30T22:25:11Z
• Authors: Claudia Feriotti; Flávio V. Loures; Eliseu Frank de A...; Tania Alves da Costa; Vera L. G. Calich
• Keywords: Mannose receptor; Mannan

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