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Characterization and therapeutic potential of chemokine action in sepsis and flavivirus-induced encephalitis

Inflammation assists in the defense against viral and bacterial infections, but needs to be tightly controlled. Indeed, an insufficient immunological response may fail to clear pathogens from the body, while overactivation or inappropriate downregulation of inflammation may lead to permanent tissue damage. Chemokines are crucial players in inflammatory reactions and are regulated by transcription and translation of chemokine ligands and receptors, posttranslational modification and interaction with glycosaminoglycans. Immunoassays quantify the total amount of a specific chemokine protein but seldom discriminate between post-translationally modified forms that often possess a different biological activity and receptor specificity. Moreover, despite current in vitro evidence that chemokine modifications and interactions with glycosaminoglycans are important, limited information is available on their role in vivo, e.g. in infection. We wish to integrate the complementary expertise of partners in Leuven and São Paulo to improve our understanding on the role of chemokines in viral and bacterial infection (using sepsis and viral encephalitis models), specifically with regard to the effect of chemokine post-translational modification and interaction with  glycosaminoglycans on the outcome of infection and inflammation. This should improve our understanding of the immune response during the infection process and eventually lead to a better drug target selection.

Date:1 Jan 2019 →  31 Dec 2021
Keywords:Medical immunology
Disciplines:Applied immunology