Abstract
Toll-like receptor (TLR) 5 has been shown to maintain intestinal homeostasis and regulate host defense against enterobacterial infection. However, how TLR5 expression is regulated and its function in the intestine have not been fully elucidated. Here we demonstrate that mucosal dendritic cells (DCs), but not splenic DCs, express high levels of TLR5 protein. Alternatively spliced Tlr5 transcripts were identified but it did not explain the selective expression of TLR5 on mucosal DCs. Treatment with various bacterial ligands downregulated BMDC TLR5 expression, while retinoic acid and host stromal cell-derived signals promoted TLR5 expression in a TGF-β-independent mechanism. Signaling through TLR5 restrained regulatory T (Treg) cell generation, and accordingly, TLR5−/− mice displayed increased frequencies of Foxp3+ Treg cells in the intestinal lamina propria. Our data indicate that bacterial and host factors differentially regulate DC TLR5 expression. TLR5 signaling regulates immune responses towards the microbiota via modulation of the Treg/effector T cell balance.
Highlights
Toll-like receptors (TLRs) recognize a variety of conserved microbial components and are able to induce innate immune responses [1]
We found that Tlr5 gene was selectively expressed at a higher level in the ileum and highest in the cecum and proximal colon than the rest of the intestinal tract (Figure 1b)
Small and large intestinal lamina propria dendritic cells (DCs) and splenic DCs were stained with anti-TLR5 antibody and analyzed by flow cytometry
Summary
Toll-like receptors (TLRs) recognize a variety of conserved microbial components and are able to induce innate immune responses [1]. They are abundantly expressed on innate cells such as macrophages, and dendritic cells (DCs), and serve as an important link between innate and adaptive immune systems. TLRs are expressed in different combinations by a wide variety of cell types, including intestinal epithelial cells (IECs), subepithelial myofibroblasts and immune cell subsets (e.g. macrophages, DCs, B cells and T cells) within the lamina propria (LP). The expression of TLRs by specific cell types differs under different local environments. Different TLR expression patterns in different locations under different environments may reflect different functional necessities of TLRligand recognition in different strategic locations [5,6]
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