Universiteit Leiden

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The Function of Toll-like receptor 2 in Infection and Inflammation

  • W. Hu
donderdag 16 december 2021
Rapenburg 73
2311 GJ Leiden


  • Prof.dr. H.P. Spaink
  • Prof.dr. F.J. Verbeek


The function of Toll-like receptors (TLRs) in innate immunity has aroused worldwide attention soon after its discovery, which was awarded a Nobel Prize in medicine in 2011. Because of the broad functions of TLR2 in innate immunity, the drive for the development of TLR2-targeted vaccines or therapeutic treatments has accelerated in the last decades. However, its dual role in both activation and suppression of innate immune responses makes it very difficult to use the available results from basic research for the development of clinical trials. In addition, it is still not clear what is the function of TLR2 in regulating phagocytic cell migration. Therefore, we aimed to determine the function of TLR2 in mycobacterial infection and explore its role in regulating phagocytic cell migration in inflammatory tissue in this thesis. For this purpose, we utilized a zebrafish larval model, which is optically transparent, genetically tractable, and contains a functional innate immune system. We showed that infection of a tlr2 mutant in zebrafish larvae leads to a higher mycobacterial burden, accompanied by a lower number of granulomas and increased extracellular bacterial growth. The role of tlr2 in controlling mycobacterial infection can be explained by reduction of mycobacterial dissemination, and modulation of anti-mycobacterial activity. Through a tail fin wounding and tail fin infection zebrafish model, we demonstrated that tlr2 is involved in modulating leukocyte migration. This thesis provides a better understanding of the functions of TLR2 in innate immune responses to infection by various mycobacterial species and wounding.


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