Study of Receptors for Histoplasma Yeasts on Murine Macrophages
Histoplasma capsulatum (Hc) is a dimorphic fungus which grows as a saprophyte in nature and is acquired by inhalation of airborne conidia and hyphal fragments. The fungus transforms to become yeast cells in the infected host. The macrophages, being the host cells, bind and ingest Hc yeasts, thereby providing the intracellular environment in which yeast cells thrive. Macrophages also act as effector cells in host defense against histoplasmosis. However, the receptors for Hc on macrophage have not been well defined, especially in mice model.
In this study, we focus on pattern recognition receptors that are able to recognize cell wall components on fungus and see if they are involved in Hc internalization by macrophage. By using an immunofluorescence staining technique to monitor the uptake of Hc yeast cells by RAW264.7 cells, we found fungal cell wall structure analogous mannan and laminarin inhibited phagocytosis of macrophages. We further used specific blocking antibody to demonstrate the identity of these receptors and found both CR3 and TLR2 were involved in Hc uptake. In subsequent experiments, we also found blocking the interaction of Hc to its receptors also abolished TNF-α production by macrophages. The results of this study contribute to the understanding of fungus entry and the roles of pattern recognition receptors in anti-fungus immune response.
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