title: Adaptive immunity against gut microbiota enhances apoE-mediated immune regulation and reduces atherosclerosis and western-diet-related inflammation.
abstract: Common features of immune-metabolic and inflammatory diseases such as metabolic syndrome, diabetes, obesity and cardiovascular diseases are an altered gut microbiota composition and a systemic pro-inflammatory state. We demonstrate that active immunization against the outer membrane protein of bacteria present in the gut enhances local and systemic immune control via apoE-mediated immune-modulation. Reduction of western-diet-associated inflammation was obtained for more than eighteen weeks after immunization. Immunized mice had reduced serum cytokine levels, reduced insulin and fasting glucose concentrations; and gene expression in both liver and visceral adipose tissue confirmed a reduced inflammatory steady-state after immunization. Moreover, both gut and atherosclerotic plaques of immunized mice showed reduced inflammatory cells and an increased M2 macrophage fraction. These results suggest that adaptive responses directed against microbes present in our microbiota have systemic beneficial consequences and demonstrate the key role of apoE in this mechanism that could be exploited to treat immune-metabolic diseases.
authors.affiliation: Microbiology and Virology Laboratory, San Raffaele Scientific Institute IRCCS, Milan, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Saita
authors.affiliation: Microbiology and Virology Laboratory, San Raffaele Scientific Institute IRCCS, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ferrarese
authors.affiliation: Cardiovascular Research Area, San Raffaele Scientific Institute IRCCS, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Foglieni
authors.affiliation: Department of Radiology, San Raffaele Scientific Institute IRCCS, Milan, Italy.|Centro Imaging Sperimentale (CIS), San Raffaele Scientific Institute IRCCS, Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Esposito
authors.affiliation: Centro Imaging Sperimentale (CIS), San Raffaele Scientific Institute IRCCS, Milan, Italy.
authors.forename: Tamara
authors.initials: T
authors.lastname: Canu
authors.affiliation: Centro Imaging Sperimentale (CIS), San Raffaele Scientific Institute IRCCS, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Perani
authors.affiliation: Department of Biotechnology and Life Sciences, Insubria University, Varese, Italy.
authors.forename: Elisa Rita
authors.initials: ER
authors.lastname: Ceresola
authors.affiliation: Microbiology and Virology Laboratory, San Raffaele Scientific Institute IRCCS, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Visconti
authors.affiliation: Microbiology and Virology Laboratory, San Raffaele Scientific Institute IRCCS, Milan, Italy.|Faculty of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Burioni
authors.affiliation: Microbiology and Virology Laboratory, San Raffaele Scientific Institute IRCCS, Milan, Italy.|Faculty of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Clementi
authors.affiliation: Microbiology and Virology Laboratory, San Raffaele Scientific Institute IRCCS, Milan, Italy.|Department of Biotechnology and Life Sciences, Insubria University, Varese, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Canducci
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001057:Apolipoproteins E / Q000097:blood / Q000502:physiology*; D050197:Atherosclerosis / Q000517:prevention & control*; D001426:Bacterial Proteins / Q000008:administration & dosage; D001786:Blood Glucose / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D066273:Diet, Western; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D006728:Hormones / Q000097:blood / Q000235:genetics; D007249:Inflammation / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018272:Porins / Q000008:administration & dosage
chemical_list: D001057:Apolipoproteins E; D001426:Bacterial Proteins; D001786:Blood Glucose; D016207:Cytokines; D006728:Hormones; D007328:Insulin; C092233:OmpK36 protein, Klebsiella pneumoniae; D018272:Porins