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

Hu, W. (2021)

Doctoral Thesis

The function of TLRs in innate immunity has aroused worldwide attention soon after its discovery. 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 by using a zebrafish larval model in this thesis. 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. 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 and tissue wounding.

• TLR2
• Mycobacterium tuberculosis
• Nontuberculous mycobacteria
• Tail wounding
• zebrafish larvae
• leukocyte biology
• Cell tracking

• All authors: Hu, W.
• Supervisor: Spaink, H.P.; Verbeek, F.J.
• Committee: Wezel, G.P. van; Snaar-Jagalska, B.E.; Merks, R.M.H.; Ottenhoff, T.H.M.; Bitter, W.
• Qualification: Doctor (dr.)
• Awarding Institution: Institute of Biology Leiden (IBL), Faculty of Science, Leiden University
• Date: 2021-12-16
• ISBN (print): 9789492597885