title: Alternative TLRs are stimulated by bacterial ligand to induce TLR2-unresponsive colon cell response.
abstract: 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.
authors.affiliation: Division of Immunology, National Institute of Cholera and Enteric Diseases, P-33, CIT Road, Scheme-XM, Kolkata 700 010, West Bengal, India.
authors.forename: Subhadeep
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Ratna
authors.initials: R
authors.lastname: Biswas
authors.forename: Tapas
authors.initials: T
authors.lastname: Biswas
mesh_terms: D051186:Armadillo Domain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003106:Colon / Q000166:cytology / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008024:Ligands; D051218:Lymphocyte Antigen 96 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018272:Porins / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D051194:Toll-Like Receptor 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051186:Armadillo Domain Proteins; D017077:Culture Media, Conditioned; D003598:Cytoskeletal Proteins; D050838:Interferon Regulatory Factor-3; C495377:LY96 protein, human; D008024:Ligands; D051218:Lymphocyte Antigen 96; D016328:NF-kappa B; D018272:Porins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C435689:SARM1 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA