title: High Fat Diet Inhibits Dendritic Cell and T Cell Response to Allergens but Does Not Impair Inhalational Respiratory Tolerance.
abstract: The incidence of obesity has risen to epidemic proportions in recent decades, most commonly attributed to an increasingly sedentary lifestyle, and a 'western' diet high in fat and low in fibre. Although non-allergic asthma is a well-established co-morbidity of obesity, the influence of obesity on allergic asthma is still under debate. Allergic asthma is thought to result from impaired tolerance to airborne antigens, so-called respiratory tolerance. We sought to investigate whether a diet high in fats affects the development of respiratory tolerance. Mice fed a high fat diet (HFD) for 8 weeks showed weight gain, metabolic disease, and alteration in gut microbiota, metabolites and glucose metabolism compared to age-matched mice fed normal chow diet (ND). Respiratory tolerance was induced by repeated intranasal (i.n.) administration of ovalbumin (OVA), prior to induction of allergic airway inflammation (AAI) by sensitization with OVA in alum i.p. and subsequent i.n. OVA challenge. Surprisingly, respiratory tolerance was induced equally well in HFD and ND mice, as evidenced by decreased lung eosinophilia and serum OVA-specific IgE production. However, in a pilot study, HFD mice showed a tendency for impaired activation of airway dendritic cells and regulatory T cells compared with ND mice after induction of respiratory tolerance. Moreover, the capacity of lymph node cells to produce IL-5 and IL-13 after AAI was drastically diminished in HFD mice compared to ND mice. These results indicate that HFD does not affect the inflammatory or B cell response to an allergen, but inhibits priming of Th2 cells and possibly dendritic cell and regulatory T cell activation.
authors.affiliation: Department of Immunology, Monash University, Melbourne, VIC 3004, Australia.|Department of Allergy, Immunology & Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, VIC 3004, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Pizzolla
authors.affiliation: Department of Immunology, Monash University, Melbourne, VIC 3004, Australia.|Department of Allergy, Immunology & Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, VIC 3004, Australia.
authors.forename: Ding Yuan
authors.initials: DY
authors.lastname: Oh
authors.affiliation: Department of Immunology, Monash University, Melbourne, VIC 3004, Australia.|Department of Allergy, Immunology & Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, VIC 3004, Australia.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Luong
authors.affiliation: Department of Immunology, Monash University, Melbourne, VIC 3004, Australia.|Department of Allergy, Immunology & Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, VIC 3004, Australia.
authors.forename: Sara R
authors.initials: SR
authors.lastname: Prickett
authors.affiliation: Baker IDI, Melbourne, VIC 3004, Australia.
authors.forename: Darren C
authors.initials: DC
authors.lastname: Henstridge
authors.affiliation: Baker IDI, Melbourne, VIC 3004, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Febbraio
authors.affiliation: Department of Immunology, Monash University, Melbourne, VIC 3004, Australia.|Department of Allergy, Immunology & Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, VIC 3004, Australia.
authors.forename: Robyn E
authors.initials: RE
authors.lastname: O'Hehir
authors.affiliation: Department of Immunology, Monash University, Melbourne, VIC 3004, Australia.|Department of Allergy, Immunology & Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, VIC 3004, Australia.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Rolland
authors.affiliation: Department of Immunology, Monash University, Melbourne, VIC 3004, Australia.|Department of Allergy, Immunology & Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, VIC 3004, Australia.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Hardy
mesh_terms: D000485:Allergens / Q000008:administration & dosage*; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000494:pharmacology*; D004802:Eosinophilia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005260:Female; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000097:blood; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D010047:Ovalbumin / Q000008:administration & dosage*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D012137:Respiratory System / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D000485:Allergens; D000534:Alum Compounds; D004041:Dietary Fats; D018793:Interleukin-13; D015848:Interleukin-5; C041524:aluminum sulfate; D007073:Immunoglobulin E; D010047:Ovalbumin