DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) is a type II C-type lectin that functions as an adhesion molecule located on dendritic cells (DCs). It enables some of the functions ofDCs, including migration, pathogen recognition, internalisation and processing, and their binding to T cells. HIV-1 has been reported to enter DCsby being bound to DC-SIGN, escaping the normal lytic pathway in DCs' endosomes and avoiding the immune system defence system. A very similar mechanism of survival has been observed for some other pathogens. This makes DC-SIGN a receptor of interest in the design of distinctive anti-infectives that would inhibit DC-SIGN-pathogen interaction by blocking the very first step in pathogen infection. In this review we outline the development of DC-SIGN antagonists, focusing mainly on a glycomimetic approach. Based on the fact that DC-SIGN binds mannose- and fucose-based oligo- and polysaccharides, their structural mimics have been designed and proved to inhibit pathogen-DC-SIGN interaction. Furthermore, recent in vitro studies have demonstrated that DC-SIGN antagonists block effectively the transmission of pathogens like HIV-1 and Ebola to CD4+ T cells. Although DC-SIGN has not been validated in vivo as a druggable target yet, we await future DC-SIGN antagonists as a new and highly promising group of novel anti-infectives.
COBISS.SI-ID: 3194737
A molecule with a relatively simple chemical structure, resveratrol has been found to interact with multiple molecular targets, many of them associated with inflammation and immunity. Indeed, it has been shown to act directly on central players of both innate and adaptive immunity, such as macrophages, lymphocytes, and dendritic cells. In addition, there is very little evidence suggesting significant deleterious side effects of resveratrol, further highlighting its potential future use as a therapeutic agent. This review provides an up-to-date discussion on recent advances regarding anti-inflammatory effects of resveratrol, mechanisms of action, and its potential for therapeutic use.
COBISS.SI-ID: 3247729
Within the complex array of numerous immunological processes that protect the host from invading pathogens and at the same time avoid excessive immune reactions with induction and maintenance of tolerance to self, the dendritic cells (DCs) have been designated as central players. Discovered and morphologically described by Steinman and Cohn almost 30 years ago, DCs have gained an ever-increasing interest from the scientific community (Steinman, Topliss et al. 1973). This has been even more pronounced throughout the last decade with the discovery that DCs not only serve as primary initiators of antigen (Ag)-specific immune responses, but can also induce immunological tolerance and contribute to immune homeostasis maintenance by various mechanisms, including induction of regulatory T cells (Treg), especially by tolerogenic DCs (Steinman, Hawiger et al. 2003). We are now witnessing the beginning of first clinical trials involving tolerogenic DCs for the treatment of immune-mediated diseases and can expect a lot of development in this field in the near future.
COBISS.SI-ID: 3203185