It includes the previously mentioned pIgR, as well as a receptor which can re-internalize IgA–antigen complexes from the gut lumen [94]. This second receptor is also expressed by M cells. Antigens complexed with IgA are addressed to DCs from PP, inducing the production of TGF-β and IL-10 [95]. There is growing evidence

that the biological process of immune tolerance to food and microbial antigens is not confined solely to lymphocytes; conversely, ZD1839 purchase all the cells in the human intestine play a role in shaping the attitude of the organism towards molecules present in the gut content. Our review emphasizes the participation of enterocytes in this orchestra of mechanisms which preserve the equilibrium

between activation and tolerance in the gut mucosa. The ultimate goal of this equilibrium is to decide more clearly when and against which it is necessary to fight back in order to preserve our BKM120 integrity as an organism. In this context, enterocytes constitute more than a physical barrier against foreign substances from the gut; they are capable of reacting intelligently to the heavy antigenic load of the gastrointestinal tract. Through their diverse array of receptors, anti-microbial peptides and regulatory cytokines, enterocytes are true immune-competent cells. The fineness of the immune mechanisms displayed by enterocytes, in conjunction with the complex design of the local lymphoid tissue, is yet to be elucidated. A better understanding of ‘who and how’ is responsible for developing oral tolerance will ultimately offer us the tools for manoeuvering in a wide range of clinical situations. This work was funded by the Romanian National Council of Scientific Research – CNCS (PD_477). The authors have no conflicts of interest to declare. “
“Little is known of how Toll-like receptor (TLR) ligands are processed after recognition by TLRs. This study was therefore designed to investigate how the TLR2 ligand FSL-1 is processed in macrophages after recognition Dichloromethane dehalogenase by TLR2. FSL-1 was internalized into the murine

macrophage cell line, RAW264.7. Both chlorpromazine and methyl-β-cyclodextrin, which inhibit clathrin-dependent endocytosis, reduced FSL-1 uptake by RAW264.7 cells in a dose-dependent manner but nystatin, which inhibits caveolae- and lipid raft-dependent endocytosis, did not. FSL-1 was co-localized with clathrin but not with TLR2 in the cytosol of RAW264.7 cells. These results suggest that internalization of FSL-1 is clathrin dependent. In addition, FSL-1 was internalized by peritoneal macrophages from TLR2-deficient mice. FSL-1 was internalized by human embryonic kidney 293 cells transfected with CD14 or CD36 but not by the non-transfected cells. Also, knockdown of CD14 or CD36 in the transfectants reduced FSL-1 uptake.