title: Lipopolysaccharide deacylation by an endogenous lipase controls innate antibody responses to Gram-negative bacteria.
abstract: T cell-independent type 1 agonists such as Gram-negative bacterial lipopolysaccharides can stimulate B lymphocytes to proliferate and produce antibodies by signaling through Toll-like receptors. This phenomenon is well established in vitro, yet polyclonal B cell responses after bacterial infection in vivo are often weak and short-lived. We show here that B cell proliferation and polyclonal antibody production in response to Gram-negative bacterial infection are modulated by acyloxyacyl hydrolase, a host enzyme that deacylates bacterial lipopolysaccharides. Deacylation of lipopolysaccharide occurred over several days, allowing lipopolysaccharide to act as an innate immune stimulant yet limiting the eventual amount of B cell proliferation and polyclonal antibody production. Control of lipopolysaccharide activation by acyloxyacyl hydrolase indicates that mammals can regulate immune responses to bacterial infection by chemical modification of a Toll-like receptor agonist.
authors.affiliation: Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Mingfang
authors.initials: M
authors.lastname: Lu
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Akira
authors.initials: A
authors.lastname: Takashima
authors.forename: Jerrold
authors.initials: J
authors.lastname: Weiss
authors.forename: Michael A
authors.initials: MA
authors.lastname: Apicella
authors.forename: Xiang-Hong
authors.initials: XH
authors.lastname: Li
authors.forename: Dorothy
authors.initials: D
authors.lastname: Yuan
authors.forename: Robert S
authors.initials: RS
authors.lastname: Munford
mesh_terms: D000107:Acetylation; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D002265:Carboxylic Ester Hydrolases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D007113:Immunity, Innate; D007114:Immunization; D008070:Lipopolysaccharides / Q000276:immunology* / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D009345:Neisseria meningitidis / Q000276:immunology*; D013154:Spleen / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D008070:Lipopolysaccharides; D002265:Carboxylic Ester Hydrolases; C048964:acyloxyacyl hydrolase