title: Intracellular Shigella remodels its LPS to dampen the innate immune recognition and evade inflammasome activation.
abstract: LPS is a potent bacterial effector triggering the activation of the innate immune system following binding with the complex CD14, myeloid differentiation protein 2, and Toll-like receptor 4. The LPS of the enteropathogen Shigella flexneri is a hexa-acylated isoform possessing an optimal inflammatory activity. Symptoms of shigellosis are produced by severe inflammation caused by the invasion process of Shigella in colonic and rectal mucosa. Here we addressed the question of the role played by the Shigella LPS in eliciting a dysregulated inflammatory response of the host. We unveil that (i) Shigella is able to modify the LPS composition, e.g., the lipid A and core domains, during proliferation within epithelial cells; (ii) the LPS of intracellular bacteria (iLPS) and that of bacteria grown in laboratory medium differ in the number of acyl chains in lipid A, with iLPS being the hypoacylated; (iii) the immunopotential of iLPS is dramatically lower than that of bacteria grown in laboratory medium; (iv) both LPS forms mainly signal through the Toll-like receptor 4/myeloid differentiation primary response gene 88 pathway; (v) iLPS down-regulates the inflammasome-mediated release of IL-1β in Shigella-infected macrophages; and (vi) iLPS exhibits a reduced capacity to prime polymorfonuclear cells for an oxidative burst. We propose a working model whereby the two forms of LPS might govern different steps of the invasive process of Shigella. In the first phases, the bacteria, decorated with hypoacylated LPS, are able to lower the immune system surveillance, whereas, in the late phases, shigellae harboring immunopotent LPS are fully recognized by the immune system, which can then successfully resolve the infection.
authors.affiliation: Dipartimento di Biologia e Biotecnologie C. Darwin and Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza-Università di Roma, 00185 Rome, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Paciello
authors.forename: Alba
authors.initials: A
authors.lastname: Silipo
authors.forename: Luigi
authors.initials: L
authors.lastname: Lembo-Fazio
authors.forename: Laura
authors.initials: L
authors.lastname: Curcurù
authors.forename: Anna
authors.initials: A
authors.lastname: Zumsteg
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Noël
authors.forename: Valeria
authors.initials: V
authors.lastname: Ciancarella
authors.forename: Luisa
authors.initials: L
authors.lastname: Sturiale
authors.forename: Antonio
authors.initials: A
authors.lastname: Molinaro
authors.forename: Maria Lina
authors.initials: ML
authors.lastname: Bernardini
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D004405:Dysentery, Bacillary / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D057131:Immune Evasion / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D058847:Inflammasomes / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D008050:Lipid A / Q000737:chemistry; D008070:Lipopolysaccharides / Q000378:metabolism*; D008954:Models, Biological; D012763:Shigella flexneri / Q000276:immunology* / Q000378:metabolism
chemical_list: D058847:Inflammasomes; D008050:Lipid A; D008070:Lipopolysaccharides
keywords: PAMPs/PRRs; enteric pathogen; immune evasion; innate immunity