The complement system is an essential component of the humoral immune system characterized by specific proteins able to bind and opsonize the whole surface of the microrganisms as bacteria, fungi and virus. These proteins induce the lysis of microrganisms by a multistep complex formation called „membrane attack complex“ (MAC). There are three different pathways for the complement activation: Classic, Alternative and Lectin pathway. All pathways are essential for the lethal complement attack on microrganisms. The complement system is tightly regulated to avoid an uncontrolled activation and lysis of human cells. The key regulator of the alternative pathway is Factor H. This protein is able to bind a specific pivotal complement protein, called C3b, in the fluid phase and on the cellular surface inhibiting the opsonization and MAC formation on human cells. Specific microrganisms have developed the ability to bind Factor H and to escape from immune complement attack.
The major opportunistic fungal species, such as Aspergillus spp, C. albicans and Mucorales spp are all able to bind Factor H on the cells wall using specific molecules. This binding decreases the lethal attack on fungi. The aim of my project is to identify these fungal molecules able to bind Factor H and to find antibodies to detect these molecules on the fungal cells. The use of these antibodies may displace bound Factor H or avoid its binding during blood dissemination. In our laboratory there are already antibodies available to detect Factor H binding molecule „high affinity glucose transporter 1” (CaHgt1p) on C. albicans using an immunofluorescence assay. We already showed by in-vitro experiments the ability of the antibodies to increase phagocytosis to C. albicans by human polymorphonuclear cells. Further studies will show whether the antibodies have a therapeutic potential.
