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Francisella tularensis LPS induces the production of cytokines in human monocytes and signals via Toll-like receptor 4 with much lower potency than E. coli LPS.
Int Immunol. 2006 May; 18(5):785-95.II

Abstract

Francisella tularensis is a virulent Gram-negative intracellular pathogen. To address the signaling routes involved in the response of host cells to LPS from F. tularensis live vaccine strain (LVS), experiments were performed in transiently transfected 293 cells. Induction of kappaB-driven transcriptional activity by 2.5 mug ml(-1) F. tularensis LPS isolated by phenol-water and ether-water extraction, was observed in cells transfected with Toll-like receptor (TLR) 4 and MD-2, although CD14 was required for optimal induction. Conversely, TLR2, TLR2/TLR1 or TLR2/TLR6 transfected cells did not show kappaB-driven transcriptional activity in the presence of F. tularensis LPS. In human monocytic cells, F. tularensis LPS activated extracellular signal-regulated kinases and the production of pro-inflammatory proteins. Concentrations of 5-10 mug ml(-1) F. tularensis LPS elicited a similar pattern of mRNA and protein induction than 0.1 mug ml(-1) E. coli LPS, including the expression of CXC chemokines (IL-8, Gro and IFN-gamma-inducible protein-10); CC chemokines (monocyte chemoattractant protein-1 and -2, macrophage-derived chemoattractant, macrophage inflammatory protein-1alpha and -1beta and RANTES (regulated upon activation, normal T cell expressed and secreted) and pro-inflammatory cytokines (IL-6 and tumor necrosis factor alpha). Altogether, these data indicate that LPS from F. tularensis LVS signals via TLR4 at higher concentrations than those required for E. coli LPS, which may explain the inflammatory reaction and the low endotoxic response associated to vaccination with LVS in humans.

Authors+Show Affiliations

Instituto de Biología y Genética Molecular, Universidad de Valladolid-CSIC, Valladolid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16574669

Citation

Dueñas, Ana I., et al. "Francisella Tularensis LPS Induces the Production of Cytokines in Human Monocytes and Signals Via Toll-like Receptor 4 With Much Lower Potency Than E. Coli LPS." International Immunology, vol. 18, no. 5, 2006, pp. 785-95.
Dueñas AI, Aceves M, Orduña A, et al. Francisella tularensis LPS induces the production of cytokines in human monocytes and signals via Toll-like receptor 4 with much lower potency than E. coli LPS. Int Immunol. 2006;18(5):785-95.
Dueñas, A. I., Aceves, M., Orduña, A., Díaz, R., Sánchez Crespo, M., & García-Rodríguez, C. (2006). Francisella tularensis LPS induces the production of cytokines in human monocytes and signals via Toll-like receptor 4 with much lower potency than E. coli LPS. International Immunology, 18(5), 785-95.
Dueñas AI, et al. Francisella Tularensis LPS Induces the Production of Cytokines in Human Monocytes and Signals Via Toll-like Receptor 4 With Much Lower Potency Than E. Coli LPS. Int Immunol. 2006;18(5):785-95. PubMed PMID: 16574669.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Francisella tularensis LPS induces the production of cytokines in human monocytes and signals via Toll-like receptor 4 with much lower potency than E. coli LPS. AU - Dueñas,Ana I, AU - Aceves,Mónica, AU - Orduña,Antonio, AU - Díaz,Ramón, AU - Sánchez Crespo,Mariano, AU - García-Rodríguez,Carmen, Y1 - 2006/03/30/ PY - 2006/4/1/pubmed PY - 2006/7/28/medline PY - 2006/4/1/entrez SP - 785 EP - 95 JF - International immunology JO - Int Immunol VL - 18 IS - 5 N2 - Francisella tularensis is a virulent Gram-negative intracellular pathogen. To address the signaling routes involved in the response of host cells to LPS from F. tularensis live vaccine strain (LVS), experiments were performed in transiently transfected 293 cells. Induction of kappaB-driven transcriptional activity by 2.5 mug ml(-1) F. tularensis LPS isolated by phenol-water and ether-water extraction, was observed in cells transfected with Toll-like receptor (TLR) 4 and MD-2, although CD14 was required for optimal induction. Conversely, TLR2, TLR2/TLR1 or TLR2/TLR6 transfected cells did not show kappaB-driven transcriptional activity in the presence of F. tularensis LPS. In human monocytic cells, F. tularensis LPS activated extracellular signal-regulated kinases and the production of pro-inflammatory proteins. Concentrations of 5-10 mug ml(-1) F. tularensis LPS elicited a similar pattern of mRNA and protein induction than 0.1 mug ml(-1) E. coli LPS, including the expression of CXC chemokines (IL-8, Gro and IFN-gamma-inducible protein-10); CC chemokines (monocyte chemoattractant protein-1 and -2, macrophage-derived chemoattractant, macrophage inflammatory protein-1alpha and -1beta and RANTES (regulated upon activation, normal T cell expressed and secreted) and pro-inflammatory cytokines (IL-6 and tumor necrosis factor alpha). Altogether, these data indicate that LPS from F. tularensis LVS signals via TLR4 at higher concentrations than those required for E. coli LPS, which may explain the inflammatory reaction and the low endotoxic response associated to vaccination with LVS in humans. SN - 0953-8178 UR - https://www.unboundmedicine.com/medline/citation/16574669/Francisella_tularensis_LPS_induces_the_production_of_cytokines_in_human_monocytes_and_signals_via_Toll_like_receptor_4_with_much_lower_potency_than_E__coli_LPS_ L2 - https://academic.oup.com/intimm/article-lookup/doi/10.1093/intimm/dxl015 DB - PRIME DP - Unbound Medicine ER -