Functional characterization of the mouse lectin ficolin-B

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Ficolins are members of the collectin family of proteins which in humans and mice are able to recognize pathogen associated molecular patterns (PAMPs) on microbial surfaces. Ficolins trigger the activation of the innate immune system by initiating the complement cascade in serum upon binding to their specific PAMPs. We recently published the first observation on mouse ficolin-B synthesis and showed that, surprisingly, the protein is localized intracellularly in macrophages. In parallel, others have shown that ficolin-B does not associate to serine proteases and, therefore, is unable to activate complement. The relevance of these findings and the mechanism of action of mouse ficolin-B upon bacterial challenge remain to be elucidated. Our preliminary data indicate that ficolin-B expression is up-regulated during activation but down-regulated during maturation of macrophages and bone marrow-derived dendritic cells suggesting a critical role of ficolin-B during early stages of cell activation upon pathogen encounter. In addition, binding assays reveal that some strains of Staph. aureus and Streptococcus pneumoniae are targets of ficolin-B. In this project we propose to study the regulation of ficolin-B expression in immune cells, the identification of its molecular target structure, and its role in cell activation. In this way, we attempt to characterize the ficolin-B-mediated innate immune response and test our hypothesis that ficolin-B plays a role in the immune response.