Obesity promotes prolonged ovalbumin-induced airway inflammation modulating T helper type 1 (Th1), Th2 and Th17 immune responses in BALB/c mice.
F M C SilvaE E OliveiraA C C GouveiaA S S BrugioloC C AlvesJ O A CorreaJ GameiroJ MattesH C TeixeiraAna Paula FerreiraPublished in: Clinical and experimental immunology (2017)
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.
Keyphrases
- high fat diet induced
- insulin resistance
- immune response
- high fat diet
- metabolic syndrome
- weight loss
- adipose tissue
- allergic rhinitis
- type diabetes
- dendritic cells
- nitric oxide synthase
- chronic obstructive pulmonary disease
- oxidative stress
- weight gain
- lung function
- nitric oxide
- bariatric surgery
- toll like receptor
- high glucose
- signaling pathway
- diabetic rats
- physical activity
- obese patients
- air pollution
- magnetic resonance imaging
- gestational age
- liver fibrosis
- regulatory t cells
- body mass index
- preterm birth
- mesenchymal stem cells
- cystic fibrosis
- drug induced
- liver injury
- case control