Laboratory of Infectious Diseases, 3rd Department of Paediatrics, School of Medicine, Aristotle University, Hippokration Hospital, Thessaloniki, Greece.
Immunol Invest. 2011;40(7-8):809-24. doi: 10.3109/08820139.2011.615877.
Phagocytic cells, particularly neutrophils and monocytes/macrophages, are the first line and the most effective form of innate host defence against pathogenic fungi. During antifungal therapy these phagocytic cells are also exposed to antifungal agents. In the phagocyte-fungus-antifungal agent interplay, drugs may directly interact with phagocytes through specific pattern recognition receptors, leading to altered antifungal activities. Antifungal agents, through modulation of fungal virulence, may initiate different immune response programs in the phagocytes, leading to antifungal synergism/antagonism or up-regulation of gene expression for a pro-inflammatory response. Additionally, indirect modulation of phagocyte behavior by pretreatment of neutrophils, monocytes, and macrophages with cytokines and exposure to antifungal agents have shown promising findings for combined drug-cytokine therapy that may improve treatment of life-threatening fungal diseases. In this review, we discuss the main in vitro and in vivo immunomodulatory effects of antifungal agents on phagocytes in response to pathogenic fungi, as well as we address underlying immunopharmacologic mechanisms and their potential impact on clinical outcome.
吞噬细胞，特别是中性粒细胞和单核细胞/巨噬细胞，是宿主防御致病性真菌的第一道也是最有效的防线。在抗真菌治疗过程中，这些吞噬细胞也会接触到抗真菌药物。在吞噬细胞-真菌-抗真菌剂的相互作用中，药物可能通过特定的模式识别受体直接与吞噬细胞相互作用，导致抗真菌活性改变。抗真菌药物通过调节真菌的毒力，可能在吞噬细胞中引发不同的免疫反应程序，导致抗真菌协同作用/拮抗作用或促炎反应的基因表达上调。此外，用细胞因子预处理中性粒细胞、单核细胞和巨噬细胞以及暴露于抗真菌药物间接调节吞噬细胞的行为，为联合药物-细胞因子治疗提供了有希望的发现，这可能改善危及生命的真菌感染疾病的治疗。在这篇综述中，我们讨论了抗真菌药物对致病性真菌作用下的吞噬细胞的主要体外和体内免疫调节作用，以及探讨了潜在的免疫药理学机制及其对临床结果的潜在影响。
