title: The Janus face of Bartonella quintana recognition by Toll-like receptors (TLRs): a review.
abstract: Bartonella quintana (B. quintana) is a facultative, intracellular bacterium, which causes trench fever, chronic bacteraemia and bacillary angiomatosis. Little is known about the recognition of B. quintana by the innate immune system. In this review, we address the impact of Toll-like receptors (TLRs) on the recognition of B. quintana and the activation of the host defense. When experimental models using human mononuclear cells, transfected CHO cells, or TLR2-/- and TLR4-/- mice were used, differential effects of TLR2 and TLR4 have been observed. B. quintana micro-organisms stimulated cytokine production through TLR2-mediated signals, whereas no role for TLR4 in the recognition of this pathogen was observed. When single, water-phenol extraction was performed, B. quintana LPS, stimulated cytokine production in a TLR2-dependent manner. However, when double extraction was performed in order to generate highly purified LPS, B. quintana LPS entirely lost its capacity to stimulate cytokines, demonstrating that non-LPS components of B. quintana are responsible for the recognition through TLR2. Moreover, B. quintana LPS was shown to be a potent antagonist of Toll-like receptor 4 (TLR4). In conclusion, B. quintana is an inducer of cytokines through TLR2-, but not TLR4-, dependent mechanisms. This stimulation is induced by bacterial components other than lipopolysaccharide. B. quintana LPS is a naturally occurring antagonist of Toll-like receptor 4 (TLR4). In view of the role played by TLR4 in inflammation, B. quintana LPS may be useful as an anti-TLR4 agent with therapeutic potential in both infections and autoimmune inflammation.
authors.affiliation: Institute of Microbiology, Department of Medical Sciences, University Magna Graecia, Via T. Campanella 115, 88100 Catanzaro, Italy. mmatera@unicz.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Matera
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Liberto
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: Maria
authors.initials: M
authors.lastname: Vinci
authors.forename: Angela
authors.initials: A
authors.lastname: Quirino
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Pulicari
authors.forename: Bart Jan
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: Jos W M
authors.initials: JW
authors.lastname: Van der Meer
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Alfredo
authors.initials: A
authors.lastname: Focà
mesh_terms: D000818:Animals; D018413:Bartonella quintana / Q000276:immunology* / Q000502:physiology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism; D014205:Trench Fever / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors