Instituto de Ciências Biomédicas, Departamento de Microbiologia, Universidade de São Paulo, São Paulo, Brazil.
BIDiagnostics, Centro de Inovação, Empreendedorismo e Tecnologia (CIETEC)/Universidade de São Paulo, São Paulo, Brazil.
Front Immunol. 2021 Oct 19;12:725882. doi: 10.3389/fimmu.2021.725882. eCollection 2021.
Monoclonal antibodies (mAbs) are promising alternatives to treat infectious diseases, especially given their potential for applications in combination therapies with antimicrobial drugs to enhance the antifungal efficacy. Protection mediated by mAbs used to treat experimental paracoccidioidomycosis (PCM) has been demonstrated previously. Our aim in the present work was to characterize a monoclonal antibody (mAbF1.4) raised against a cell wall glycoconjugate fraction of spp. and to analyze its efficacy combined with trimethoprim-sulfamethoxazole (TMP/SMX) as treatment for experimental PCM. We demonstrated that the epitope recognized by mAbF1.4 is consistent with branched glucose residues present on a cell wall β-glucan polymer. , mAbF1.4 increased the phagocytic capacity and nitric oxide concentration induced by the macrophage cell line J774.1A, and this resulted in a significant reduction in the viability of the opsonophagocytized yeasts. , we detected a significant reduction in pulmonary fungal burdens of mice treated with mAbF1.4 in association with TMP/SMX, which correlated with increased pulmonary concentrations (determined by ELISA) of IFN- γ, TNF-α, IL-10 and IL-17. In parallel, we observed a decrease in IL-4, suggesting that the treatment was associated with a mixed Th1-Th17 type immune response. Histopathology of lung segments from mice receiving the combination therapy showed a significant reduction in granulomas, which were well-defined, and improved maintenance of lung architecture. These findings demonstrate that mAbF1.4 + TMP/SMX therapy is a promising approach to combat PCM as well as decrease disease sequelae and highlights the potential benefits of immune mediators in PCM combined immunotherapy.
单克隆抗体（mAbs）是治疗传染病的有前途的替代品，尤其是考虑到它们在与抗微生物药物联合治疗中的应用潜力，以提高抗真菌功效。先前已经证明了用于治疗实验性副球孢子菌病（PCM）的 mAbs 介导的保护作用。我们在本工作中的目的是表征针对 spp.细胞壁糖缀合物部分的单克隆抗体（mAbF1.4），并分析其与复方新诺明（TMP/SMX）联合治疗实验性 PCM 的疗效。我们证明了 mAbF1.4 识别的表位与细胞壁β-葡聚糖聚合物上存在的分支葡萄糖残基一致。 ，mAbF1.4 增加了巨噬细胞系 J774.1A 的吞噬能力和诱导的一氧化氮浓度，导致被调理的酵母的活力显著降低。 ，我们检测到与 TMP/SMX 联合使用 mAbF1.4 治疗的小鼠肺部真菌负担显着降低，这与 IFN-γ、TNF-α、IL-10 和 IL-17 的肺部浓度增加（通过 ELISA 确定）相关。平行地，我们观察到 IL-4 减少，表明治疗与混合 Th1-Th17 型免疫反应有关。接受联合治疗的小鼠肺段的组织病理学显示，肉芽肿明显减少，并且维持肺结构的能力得到改善。这些发现表明，mAbF1.4+TMP/SMX 治疗是一种有前途的治疗 PCM 的方法，可减少疾病后遗症，并强调了免疫调节剂在 PCM 联合免疫治疗中的潜在益处。
