Complement Receptor 3, Cell Surface Glycans, and Dectin‐1 Have Distinct Functions in the Phagocytosis and Cytokine Responses by Macrophage to Histoplasma capsulatum

Histoplasma capsulatum is a dimorphic intracellular fungal pathogen. The yeast cell takes primary residence within the macrophages. Thus, the interaction with macrophage is vital to the pathogenesis of Histoplasma infection, the receptor(s) for Histoplasma entering the macrophage and that triggering cytokine response remains largely unclear. In this study, we showed that complement receptor 3 (CR3), but not β‐glucan receptor Dectin‐1, TLR2, TLR4, FcγR or mannose receptor, mediates macrophage phagocytosis of Histoplasma . Furthermore, macrophages pretreated with sialidase, heparin, or fibronectin efficiently blocked phagocytosis, indicating that cell surface glycans also play an important role in macrophage‐ Histoplasma interaction. Interestingly, combined treatment with anti‐CR3 Ab and sialidase or heparin completely inhibited macrophage phagocytosis. These results strongly indicate that CR3 and cell surface glycans are the receptors that corporately mediate binding and internalization of Histoplasma on murine macrophages. We next examined whether interference with phagocytosis also affects Histoplasma ‐induced cellular response, specifically cytokine production. CR3 was also involved in macrophage TNF‐α and IL‐6 responses. Interestingly, although Dectin‐1 played no role in the phagocytosis of Histoplasma , it was important to macrophage cytokine responses. These data together showed that CR3, cell surface glycans, and Dectin‐1 have distinct roles in macrophage responses to Histoplasma . This work was supported by NSC Grants 94‐2320‐B‐002‐064 and 95‐2320‐B‐002‐027.