Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan.
J Leukoc Biol. 2010 Jul;88(1):95-106. doi: 10.1189/jlb.1109717. Epub 2010 Apr 1.
The yeast cells of dimorphic fungal pathogen Histoplasma reside primarily within the macrophages of an infected host; the interaction between the yeast and macrophage has a profound impact on host defense against the fungus. We used blocking antibodies and saccharides to identify the receptors that participate in the phagocytosis of and the cytokine response to Histoplasma. The phagocytosis and cytokine response results show that sialic acids on the macrophages were involved in the interaction between macrophages and Histoplasma. CR3, although not the only receptor involved, was responsible for phagocytosis and cytokine response. It is unclear which receptors other than CR3 are responsible for phagocytosis, but we did rule out the participation of TLR2, TLR4, MR, DC-SIGN/SIGNR1, FcgammaR, VLA-5, and Dectin-1. Even though Dectin-1 did not participate in phagocytosis, it collaborated with CR3 in the cytokine response to Histoplasma, suggesting that in the presence of phagocytic receptors, Histoplasma triggers cytokine signals through Dectin-1. Moreover, macrophage phagocytosis of and cytokine response to Histoplasma are Syk kinase-dependent. Our study delineated the distinct roles of CR3, Dectin-1, and sialic acids in the interaction with Histoplasma and suggested that multiple receptor use might be important to host defense against Histoplasma.
双相真菌病原体组织胞浆菌的酵母细胞主要存在于受感染宿主的巨噬细胞内；酵母和巨噬细胞之间的相互作用对宿主防御真菌具有深远的影响。我们使用阻断抗体和糖来鉴定参与组织胞浆菌吞噬作用和细胞因子反应的受体。吞噬作用和细胞因子反应结果表明，巨噬细胞上的唾液酸参与了巨噬细胞与组织胞浆菌之间的相互作用。CR3 虽然不是参与的唯一受体，但负责吞噬作用和细胞因子反应。尚不清楚除 CR3 以外还有哪些受体负责吞噬作用，但我们排除了 TLR2、TLR4、MR、DC-SIGN/SIGNR1、FcγR、VLA-5 和 Dectin-1 的参与。尽管 Dectin-1 不参与吞噬作用，但它与 CR3 一起参与了对组织胞浆菌的细胞因子反应，这表明在存在吞噬受体的情况下，组织胞浆菌通过 Dectin-1 触发细胞因子信号。此外，巨噬细胞对组织胞浆菌的吞噬作用和细胞因子反应依赖于 Syk 激酶。我们的研究描绘了 CR3、Dectin-1 和唾液酸在与组织胞浆菌相互作用中的独特作用，并表明多种受体的使用可能对宿主防御组织胞浆菌至关重要。
