Marques Alexandre F, da Silva Marcelo B, Juliano Maria A P, Munhõz Julian E, Travassos Luiz R, Taborda Carlos P
Institute of Biomedical Sciences, Department of Microbiology, University of São Paulo, São Paulo, SP, Brazil.
Microbes Infect. 2008 Oct;10(12-13):1251-8. doi: 10.1016/j.micinf.2008.07.027. Epub 2008 Jul 24.
Paracoccidioidomycosis is a systemic granulomatous disease manifested in the acute/subacute or chronic forms. The anergic cases of the acute/subacute form are most severe, leading to death threatening conditions. Drug treatment is required to control the disease but the response in anergic patients is generally poor. A 15-mer peptide from the major diagnostic antigen gp43, named P10, induces a T-CD4+ helper-1 immune response in mice of different haplotypes and protects against intratracheal challenge with virulent P. brasiliensis. Presently, P10 immunization and chemotherapy were associated in an attempt to improve antifungal treatment in Balb/c mice made anergic by adding dexamethasone to the drinking water. The combined drug/peptide treatment significantly reduced the lung CFUs in infected anergic mice, largely preserved lung alveolar structure and prevented fungal dissemination to liver and spleen. Results recommend that a P10-based vaccine should be associated to chemotherapy for improved treatment of paracoccidioidomycosis aiming especially at anergic cases.
副球孢子菌病是一种表现为急性/亚急性或慢性形式的全身性肉芽肿疾病。急性/亚急性形式的无反应性病例最为严重，可导致危及生命的状况。需要药物治疗来控制疾病，但无反应性患者的反应通常较差。来自主要诊断抗原gp43的一种15肽，名为P10，可在不同单倍型的小鼠中诱导T-CD4+辅助性1型免疫反应，并保护小鼠免受巴西副球孢子菌气管内攻击。目前，将P10免疫与化疗联合使用，试图改善通过在饮用水中添加地塞米松使Balb/c小鼠产生无反应性后的抗真菌治疗。联合药物/肽治疗显著降低了感染无反应性小鼠肺部的菌落形成单位，很大程度上保留了肺泡结构，并防止真菌扩散到肝脏和脾脏。结果表明，基于P10的疫苗应与化疗联合使用，以改善副球孢子菌病的治疗，尤其针对无反应性病例。
