Characterization of the molecular basis underlying the subversion of dendritic cells homoeostasis by implantable biomaterials
Year: 2011
Type: dissertation
Abstract: In modern medicine, biomaterials are used in several medical applications ranging from tissue regeneration to antigen-delivery systems. Despite the widespread use of biomaterials, the reaction of the host immune system against implants still constitutes a problem sometime causing implant failure. Thus, there is a major need to understand how biomaterials interact with the immune cells. Dendritic cells (DCs) are the specialized antigen-presenting cells that have the unique ability to sense intruding pathogens, activate naïve antigen-specific T cells and regulate immunological responses. In this study, I have analyzed the molecular interactions between chemically and physically diverse biomaterials and DCs using several murine knockout systems. I found that DCs could sense biomedical polymers through a mechanism, which involves multiple TLR/MyD88-dependent signalling pathways, in particular TLR2, TLR4 and TLR6. TLR-biomaterial interactions induce the expression of activation markers and pro-inflammatory cytokines and are sufficient to confer on DCs the ability to activate antigen-specific T cells. This takes place through direct biomaterial-DC interactions although, for degradable biomaterials, soluble polymer molecules can also alter DC function. Finally, the engagement of TLRs by biomaterials profoundly alters DC adhesive properties. These findings should be useful for designing structure-function studies aimed at developing more bio-inert materials. Moreover, given the major role of TLR2, TLR4 and TLR6 in the alteration of DC functions by biomaterials shown in this work, I also envisage the possibility to design biomaterials that specifically activate TLR2 or TLR4 to achieve antigen-specific TH1- or TH2-type immune responses, respectively.
Source: RWTH Publications (RWTH Aachen)
Authors: Behnaz Shokouhi, Martin Zenke
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W940972398