The consequences of multiple simulatancous C-type lectin-ligand interactions: DCIR alters the endo-lysosomal routing of DC-SIGN

Autor: García-Vallejo, Juan J, Bloem, Karien, Knippels, Léon M J, Garssen, Johan, van Vliet, Sandra J, van Kooyk, Yvette, Sub General Pharmacology, Sub Immunopharmacology, Pharmacology
Přispěvatelé: Molecular cell biology and Immunology, CCA - Immuno-pathogenesis, Sub General Pharmacology, Sub Immunopharmacology, Pharmacology
Rok vydání: 2015
Předmět:
Zdroj: Frontiers in Immunology
Frontiers in Immunology [E], 6. Frontiers Media S.A.
Frontiers in Immunology, Vol 6 (2015)
Frontiers in Immunology: Molecular Innate Immunity, 6:87. Frontiers Media S.A.
Garcia Vallejo, J J, Bloem, K, Knippels, L M J, Garssen, J, van Vliet, S J & van Kooyk, Y 2015, ' The consequences of multiple simulatancous C-type lectin-ligand interactions: DCIR alters the endo-lysosomal routing of DC-SIGN ', Frontiers in Immunology: Molecular Innate Immunity, vol. 6, 87 . https://doi.org/10.3389/fimmu.2015.00087
ISSN: 1664-3224
DOI: 10.3389/fimmu.2015.00087
Popis: Antigen-presenting cells (APCs) are equipped with multiple receptors to allow proper pathogen recognition and capture. C-type lectin receptors (CLRs) recognize glycan struc- tures on pathogens and endogenous glycoproteins for internalization and antigen process- ing and presentation. Often, the glycan specificity of these receptors is overlapping and/or pathogens are decorated with ligands for multiple CLRs, posing the question whether interference or cooperativity within the CLR family exists. Here, we used imaging flow cytometry to investigate the internalization properties of four different CLRs (mannose receptor, DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), macrophage galactose-type lectin, and dendritic cell immunoreceptor (DCIR)) on different APCs, as well as their intracellular routing. Although the internalization score of the inves- tigated CLRs was similar on monocytes, macrophages, and dendritic cells (DCs), DCIR internalization rates were lower compared to the other CLRs. Upon triggering, DCIR routed to intracellular compartments outside of the classical endo-lysosomal pathway, resulting in poor CD4 C T-cell stimulation. Although DC maturation reduced CLR expression levels, it did not affect their internalization rates. Although CLR internalization appeared to be independently regulated, DC-SIGN routing was affected when DCIR was triggered simul- taneously. In conclusion, our results provide new insights for the design of DC-based immunotherapeutic strategies and suggest that DCIR is an inferior target in this respect.
Databáze: OpenAIRE