title: Temperature-dependent modulation of Porphyromonas gingivalis lipid A structure and interaction with the innate host defenses.
abstract: Lipid A structure is a critical determinant of the interaction between pathogens and the innate immune system. Previously, we demonstrated the presence of non- and monophosphorylated tetra-acylated lipid A structures in the outer membrane of Porphyromonas gingivalis, an agent of human periodontal disease. These modifications to lipid A structure lead to evasion and suppression of innate defenses mediated by Toll-like receptor 4 (TLR4) and cationic antimicrobial peptides. In this investigation, we examined the influence of growth temperature on P. gingivalis lipid A structure and recognition by TLR4 as an example of an environmental influence which is known to vary between healthy and diseased sites in the periodontium. We demonstrate that P. gingivalis grown at a normal body temperature produces mainly nonphosphorylated and monophosphorylated tetra-acylated lipid A structures, whereas bacteria grown at 39°C and 41°C intended to mimic increasing levels of inflammation, producing increasing proportions of monophosphorylated, penta-acylated lipid A. The temperature-dependent alteration in lipid A renders the bacterium significantly more potent for activating TLR4 and more susceptible to killing by β-defensins 2 and 3. This is the first report of a lipid A remodeling system linked to temperature shifts associated with a deregulated inflammatory response. Temperature elevation at sites of inflammation in the periodontium may be a significant environmental regulator of the lipid A modification systems of P. gingivalis, which will influence the interaction of this organism with the innate host defense.
authors.affiliation: Centre for Immunology and Infectious Disease, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London E1 2AT, United Kingdom. M.A.Curtis@qmul.ac.uk
authors.forename: Michael A
authors.initials: MA
authors.lastname: Curtis
authors.forename: Rimondia S
authors.initials: RS
authors.lastname: Percival
authors.forename: Deirdre
authors.initials: D
authors.lastname: Devine
authors.forename: Richard P
authors.initials: RP
authors.lastname: Darveau
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Coats
authors.forename: Minnie
authors.initials: M
authors.lastname: Rangarajan
authors.forename: Edward
authors.initials: E
authors.lastname: Tarelli
authors.forename: Philip D
authors.initials: PD
authors.lastname: Marsh
mesh_terms: D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008050:Lipid A / Q000737:chemistry* / Q000276:immunology*; D016966:Porphyromonas gingivalis / Q000737:chemistry / Q000254:growth & development* / Q000276:immunology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013696:Temperature; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D023083:beta-Defensins / Q000378:metabolism
chemical_list: C106641:DEFB4A protein, human; D008050:Lipid A; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D023083:beta-Defensins