Quinello Camila, Souza Ferreira Lucas, Picolli Isabella, Loesch Maria Luiza, Portuondo Deivys Leandro, Batista-Duharte Alexander, Zeppone Carlos Iracilda
Department of Clinical Analysis, School of Pharmaceutical Sciences, Araraquara, São Paulo State University (UNESP), Rodovia Araraquara-Jaú-Km 1, Araraquara 14800-903, SP, Brazil.
J Fungi (Basel). 2018 Sep 2;4(3):106. doi: 10.3390/jof4030106.
Sporotrichosis is a subcutaneous mycosis affecting humans and other animals. The disease can be acquired by accidental inoculation of the fungus through the skin or through the respiratory system. Sporotrichosis can also be transmitted through bites or scratches by infected cats and more rarely by other animals (zoonotic transmission). Conventional antifungal therapy is especially inefficient in immunocompromised patients, who tend to develop the most severe forms of the disease, thus prompting the search for alternative therapies. Given their antigen-presenting properties, dendritic cells (DCs) have been used in both prophylactic and therapeutic vaccination strategies. Hence, this study aims to assess the use of DCs as a prophylactic tool in sporotrichosis by evaluating the immune profile induced by cell wall proteins (SsCWP)-stimulated, bone-marrow-derived DCs (BMDCs). Mouse BMDCs were stimulated with SsCWP for 24 h and analyzed for the surface expression of costimulatory molecules and TLR-4, as well as for the secretion of proinflammatory cytokines and IL-10. Following that, activated BMDCs were cocultured with splenocytes for 72 h and had the same cytokines measured in the supernatant. SsCWP-stimulated BMDCs showed higher expression of CD80, CD86, and CD40, but not TLR-4, and higher secretion of IL-6, IL-17A, and TNF. On the other hand, higher levels of IFN-γ, IL-10, and IL-2 were found in the supernatants of the coculture as compared with the BMDCs alone; TNF secretion was almost completely abrogated, whereas IL-6 was only partially inhibited and IL-17A was unaffected. Our results thus suggest that SsCWP-stimulated BMDCs are able to induce a Th1-prone cytokine profile which is known to be protective against other fungal diseases. This result could lead to studies which evaluate the development of prophylactic and/or therapeutic DC-based tools against sporotrichosis.
孢子丝菌病是一种影响人类和其他动物的皮下真菌病。该疾病可通过真菌经皮肤意外接种或通过呼吸系统感染获得。孢子丝菌病也可通过受感染猫的咬伤或抓伤传播，很少通过其他动物传播（人畜共患病传播）。传统的抗真菌疗法在免疫功能低下的患者中尤其无效，这些患者往往会发展为最严重的疾病形式，因此促使人们寻找替代疗法。鉴于其抗原呈递特性，树突状细胞（DCs）已被用于预防性和治疗性疫苗接种策略。因此，本研究旨在通过评估细胞壁蛋白（SsCWP）刺激的骨髓来源的DCs（BMDCs）诱导的免疫谱，来评估DCs作为孢子丝菌病预防性工具的用途。用SsCWP刺激小鼠BMDCs 24小时，分析共刺激分子和TLR-4的表面表达，以及促炎细胞因子和IL-10的分泌。随后，将活化的BMDCs与脾细胞共培养72小时，并测量上清液中相同的细胞因子。SsCWP刺激的BMDCs显示出CD80、CD86和CD40的表达较高，但TLR-4不高，并且IL-6、IL-17A和TNF的分泌较高。另一方面，与单独的BMDCs相比，共培养上清液中发现IFN-γ、IL-10和IL-2的水平更高；TNF分泌几乎完全被消除，而IL-6仅被部分抑制，IL-17A未受影响。因此，我们的结果表明，SsCWP刺激的BMDCs能够诱导倾向于Th1的细胞因子谱，已知该谱对其他真菌疾病具有保护作用。这一结果可能会促使开展研究，评估针对孢子丝菌病的基于DCs的预防性和/或治疗性工具的开发。
