Alternative TLRs are stimulated by bacterial ligand to induce TLR2-unresponsive colon cell response

• Published in: Cellular signalling 2013-08, Vol.25 (8), p.1678-1688
• Main Authors: Mukherjee, Subhadeep, Biswas, Ratna, Biswas, Tapas
• Format: Article
• Language: English
• Subjects: Armadillo Domain Proteins - antagonists & inhibitors; Armadillo Domain Proteins - genetics; Armadillo Domain Proteins - metabolism; Bacteria; Cell Line; Cell Movement - drug effects; Colon - cytology; Colon - metabolism; Colon cells; Culture Media, Conditioned - pharmacology; Cytoskeletal Proteins - antagonists & inhibitors; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; HEK293 Cells; HT29 Cells; Humans; Innate response; Interferon Regulatory Factor-3 - metabolism; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - metabolism; Ligands; Lymphocyte Antigen 96 - genetics; Lymphocyte Antigen 96 - metabolism; NF-kappa B - metabolism; Porin; Porins - pharmacology; RNA Interference; RNA, Messenger - metabolism; RNA, Small Interfering - metabolism; Signal Transduction; Toll-Like Receptor 1 - antagonists & inhibitors; Toll-Like Receptor 1 - genetics; Toll-Like Receptor 1 - metabolism; Toll-Like Receptor 2 - antagonists & inhibitors; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 4 - antagonists & inhibitors; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Transcription Factor RelA - metabolism; Up-Regulation - drug effects
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2013.04.008

Although pathogenic bacteria penetrate colonic cells causing infection, the role of its surface molecules serving as key Toll-like receptor (TLR) ligands and triggering response remains unexplored. We show that TLR2-ligand porin up-regulated TLR4 on HT-29 cells, which the TLR4-ligand LPS could not. TLR1 that co-express with TLR2 got stimulated with TLR4. Besides the two TLRs, MD-2 was expressed revealing that the TLR4 co-receptor is not exclusive for LPS signaling. SARM-1 that mostly down-regulates TLR-signaling, demonstrated central role in signaling by engaging IRF-3 and NF-κB for cell activity. Porin induced type 1 chemokines particularly MCP-3, while porin-stimulated HT-29 culture supernatant displayed PBMC migration, collectively suggesting that the chemokines influence colon and immune cell cross-talk. In TLR2 down-regulated HT-29 cells, we found TLR1 and TLR4 as substitute TLRs to identify porin and orchestrate signaling. Thus, TLR replacement for PAMP recognition demonstrates specificity of ligand·TLR association can compromise and is a necessary alternative for successful execution of immune responses. [Display omitted] •TLR2-ligand porin stimulated TLR1 and TLR4 of TLR2 down-regulated HT-29 cells.•Porin induced MD-2, the TLR4 co-receptor known for LPS mediated signaling.•SARM-1 showed central role in TLR signaling for colonic HT-29 cell response.•Chemokine expression of the colon cells putatively regulated immune cell migration.