Laboratory of Clinical Immunology, School of Pharmaceutical Sciences, São Paulo State University, São Paulo, Brazil.
Mycopathologia. 2012 Jul;174(1):21-30. doi: 10.1007/s11046-012-9523-1.
For many fungal diseases, macrophages are the major cell population implicated in host protection, primarily by their ability to eliminate the invading fungal pathogen through phagocytosis. In sporotrichosis, this remains true, because of macrophages’ ability to recognize Sporothrix schenckii through specific receptors for some of the fungus’ cellular surface constituents. Further confirmation for macrophages’ pivotal role in fungal diseases came with the identification of toll-like receptors, and the subsequent numerous associations found between TLR-4 deficiency and host susceptibility to diverse fungal pathogens. Involvement of TLR-4 in immune response against sporotrichosis has been conducted to investigate how TLR-4 signaling could affect inflammatory response development through evaluation of H2O2 production and IL-1β, IL-6 and TGF-β release during the course of S. schenckii infection on TLR-4-deficient mice. The results showed that macrophages are largely dependent on TLR-4 for inflammatory activation and that in the absence of TLR-4 signaling, increased TGF-β release may be one of the contributing factors for the abrogated inflammatory activation of peritoneal exudate cells during mice sporotrichosis.
对于许多真菌感染性疾病而言,巨噬细胞是宿主防御的主要细胞群体,这主要是因为它们能够通过吞噬作用来消灭入侵的真菌病原体。在孢子丝菌病中,情况仍然如此,这是因为巨噬细胞能够通过识别孢子丝菌细胞表面某些成分的特定受体来识别孢子丝菌。随着 Toll 样受体的鉴定以及随后在 TLR-4 缺陷与宿主对各种真菌病原体易感性之间发现了众多关联,进一步证实了巨噬细胞在真菌感染性疾病中的关键作用。对 TLR-4 在孢子丝菌病免疫反应中的作用进行了研究,以探讨 TLR-4 信号通路如何通过评估 H2O2 产生以及在 TLR-4 缺陷小鼠感染孢子丝菌过程中 IL-1β、IL-6 和 TGF-β 的释放来影响炎症反应的发展。结果表明,巨噬细胞在很大程度上依赖 TLR-4 来实现炎症激活,并且在 TLR-4 信号通路缺失的情况下,TGF-β 的释放增加可能是导致小鼠孢子丝菌病时腹腔渗出细胞炎症激活被阻断的一个因素。