Pizzolla Angela, Oh Ding Yuan, Luong Suzanne, Prickett Sara R, Henstridge Darren C, Febbraio Mark A, O'Hehir Robyn E, Rolland Jennifer M, Hardy Charles L
Department of Immunology, Monash University, Melbourne, VIC 3004, Australia.
Department of Allergy, Immunology & Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, VIC 3004, Australia.
PLoS One. 2016 Aug 2;11(8):e0160407. doi: 10.1371/journal.pone.0160407. eCollection 2016.
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.
近几十年来，肥胖症的发病率已上升到流行程度，最常见的原因是久坐不动的生活方式日益普遍，以及高脂肪、低纤维的“西方”饮食。尽管非过敏性哮喘是肥胖症一种公认的合并症，但肥胖对过敏性哮喘的影响仍存在争议。过敏性哮喘被认为是由于对空气传播抗原的耐受性受损，即所谓的呼吸道耐受性受损所致。我们试图研究高脂肪饮食是否会影响呼吸道耐受性的发展。与喂食正常食物饮食（ND）的年龄匹配小鼠相比，喂食高脂肪饮食（HFD）8周的小鼠体重增加、出现代谢疾病，并且肠道微生物群、代谢物和葡萄糖代谢发生改变。在通过腹腔注射明矾中的卵清蛋白（OVA）致敏并随后进行鼻内OVA激发诱导过敏性气道炎症（AAI）之前，通过反复鼻内（i.n.）给予卵清蛋白（OVA）诱导呼吸道耐受性。令人惊讶的是，HFD小鼠和ND小鼠诱导呼吸道耐受性的效果相同，肺嗜酸性粒细胞减少和血清OVA特异性IgE产生减少证明了这一点。然而，在一项初步研究中，与诱导呼吸道耐受性后的ND小鼠相比，HFD小鼠的气道树突状细胞和调节性T细胞活化有受损的趋势。此外，与ND小鼠相比，HFD小鼠在AAI后淋巴结细胞产生IL-5和IL-13的能力大幅下降。这些结果表明，HFD不会影响对过敏原的炎症反应或B细胞反应，但会抑制Th2细胞的启动以及可能的树突状细胞和调节性T细胞活化。
