title: Obesity promotes prolonged ovalbumin-induced airway inflammation modulating T helper type 1 (Th1), Th2 and Th17 immune responses in BALB/c mice.
abstract: Clinical and epidemiological studies indicate that obesity affects the development and phenotype of asthma by inducing inflammatory mechanisms in addition to eosinophilic inflammation. The aim of this study was to assess the effect of obesity on allergic airway inflammation and T helper type 2 (Th2) immune responses using an experimental model of asthma in BALB/c mice. Mice fed a high-fat diet (HFD) for 10 weeks were sensitized and challenged with ovalbumin (OVA), and analyses were performed at 24 and 48 h after the last OVA challenge. Obesity induced an increase of inducible nitric oxide synthase (iNOS)-expressing macrophages and neutrophils which peaked at 48 h after the last OVA challenge, and was associated with higher levels of interleukin (IL)-4, IL-9, IL-17A, leptin and interferon (IFN)-γ in the lungs. Higher goblet cell hyperplasia was associated with elevated mast cell influx into the lungs and trachea in the obese allergic mice. In contrast, early eosinophil influx and lower levels of IL-25, thymic stromal lymphopoietin (TSLP), CCL11 and OVA-specific immunoglobulin (IgE) were observed in the obese allergic mice in comparison to non-obese allergic mice. Moreover, obese mice showed higher numbers of mast cells regardless of OVA challenge. These results indicate that obesity affects allergic airway inflammation through mechanisms involving mast cell influx and the release of TSLP and IL-25, which favoured a delayed immune response with an exacerbated Th1, Th2 and Th17 profile. In this scenario, an intense mixed inflammatory granulocyte influx, classically activated macrophage accumulation and intense mucus production may contribute to a refractory therapeutic response and exacerbate asthma severity.
authors.affiliation: Department of Parasitology, Microbiology, and Immunology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil.
authors.forename: F M C
authors.initials: FMC
authors.lastname: Silva
authors.affiliation: Department of Parasitology, Microbiology, and Immunology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil.
authors.forename: E E
authors.initials: EE
authors.lastname: Oliveira
authors.affiliation: Department of Parasitology, Microbiology, and Immunology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil.
authors.forename: A C C
authors.initials: ACC
authors.lastname: Gouveia
authors.affiliation: Department of Parasitology, Microbiology, and Immunology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil.
authors.forename: A S S
authors.initials: ASS
authors.lastname: Brugiolo
authors.affiliation: Federal University of Vales do Jequitinhonha e Mucuri, Medicial School do Mucuri, FAMMUC, São Paulo, MG, Brazil.
authors.forename: C C
authors.initials: CC
authors.lastname: Alves
authors.affiliation: Department of Pharmaceutics Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil.
authors.forename: J O A
authors.initials: JOA
authors.lastname: Correa
authors.affiliation: Department of Parasitology, Microbiology, and Immunology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil.
authors.forename: J
authors.initials: J
authors.lastname: Gameiro
authors.affiliation: Centre for Asthma and Respiratory Diseases and Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Mattes
authors.affiliation: Department of Parasitology, Microbiology, and Immunology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil.
authors.forename: H C
authors.initials: HC
authors.lastname: Teixeira
authors.affiliation: Department of Parasitology, Microbiology, and Immunology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil.
authors.forename: A P
authors.identifier: 0000-0002-0020-1828
authors.initials: AP
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology*; D010047:Ovalbumin; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D007073:Immunoglobulin E; D010047:Ovalbumin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse
keywords: BALB/c mice; asthma; eosinophils; high-fat diet; neutrophils; obesity