Obesity shifts house dust mite-induced airway cellular infiltration from eosinophils to macrophages: effects of glucocorticoid treatment

Diaz, Jennifer; Warren, L.K.; Helfner, Laura; Xue, Xiangying; Chatterjee, Prodyot K.; Gupta, Madhu; Solanki, Malvika H.; Esposito, Michael; Bonagura, Vincent R.; Metz, Christine N.

doi:10.1007/s12026-015-8717-2

Cited by 28 publications

(24 citation statements)

References 66 publications

(70 reference statements)

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“…We found that short‐term HFD feeding in OVA mice reduced neither airway nor tissue eosinophil numbers. In contrast, in obese mice (>35 g body weight), experimental allergen‐ or diesel particulate‐induced allergic asthma was associated with a lower airway eosinophilia, but a higher recruitment of tissue‐associated eosinophils as compared to lean mice . In addition, HFD‐driven increases in leptin concentration impaired the recruitment of eosinophils into the airways .…”

Section: Discussionmentioning

confidence: 87%

Short‐term high‐fat diet feeding protects from the development of experimental allergic asthma in mice

Schröder

Wiese

Ender

et al. 2019

Clin Experimental Allergy

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Background A close association between obesity and asthma has been described. The nature of this association remains elusive, especially with respect to allergic asthma. Controversial findings exist regarding the impact of short‐term high‐fat diet (HFD) feeding on the development of allergic asthma. Objective To delineate the impact of short‐term HFD feeding on the development of experimental allergic asthma. Methods Female C57BL/6JRJ mice were fed with a short‐term HFD or chow diet (CD) for 12 weeks. Allergic asthma was induced by intraperitoneal OVA/alum sensitization followed by repeated OVA airway challenges. We determined airway hyperresponsiveness (AHR) and pulmonary inflammation by histologic and flow cytometric analysis of immune cells. Furthermore, we assessed the impact of HFD on dendritic cell (DC)‐mediated activation of T cells. Results Female mice showed a mild increase in body weight accompanied by mild metabolic alterations. Upon OVA challenge, CD‐fed mice developed strong AHR and airway inflammation, which were markedly reduced in HFD‐fed mice. Mucus production was similar in both treatment groups. OVA‐induced increases in DC and CD4+ T‐cell recruitment to the lungs were significantly attenuated in HFD‐fed mice. MHC‐II expression and CD40 expression in pulmonary CD11b+ DCs were markedly lower in HFD‐fed compared to CD‐fed mice, which was associated in vivo with a decreased T helper (Th) 1/17 differentiation and Treg formation without impacting Th2 differentiation. Conclusions/clinical relevance These findings suggest that short‐term HFD feeding attenuates the development of AHR, airway inflammation, pulmonary DC recruitment and MHC‐II/CD40 expression leading to diminished Th1/17 but unchanged Th2 differentiation. Thus, short‐term HFD feeding and associated metabolic alterations may have protective effects in allergic asthma development.

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Section: Discussionmentioning

confidence: 87%

Short‐term high‐fat diet feeding protects from the development of experimental allergic asthma in mice

Schröder

Wiese

Ender

et al. 2019

Clin Experimental Allergy

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“…In humans with severe asthma, classically activated macrophages are associated with corticosteroid resistance [45,46]. According to previous studies, obesity can induce a switch from an M2 macrophage phenotype towards a more M1 macrophage phenotype in obese allergic mice [20,47]. Furthermore, the enhanced and continuous influx of macrophages into the airways of obese allergic mice suggests the persistent activation of innate immunity and a potential role of M1 polarized macrophages in maintaining inflammation in the lungs by releasing IL-1b, IL-6 and TNF-a.…”

Section: Discussionmentioning

confidence: 95%

“…Studies involving animal models support the association between obesity and asthma; however, these studies have provided conflicting results, due probably to the use of different protocols and mouse strains for inducing both diseases . A study employing obesity‐prone C57BL/6 mice indicated that obesity exacerbates the asthma pathology via a Th2 immune response mechanism , which was not supported by other studies . BALB/c mice represent an intermediate phenotype between the obesity‐prone and resistant strain.…”

Section: Introductionmentioning

confidence: 99%

Obesity promotes prolonged ovalbumin-induced airway inflammation modulating T helper type 1 (Th1), Th2 and Th17 immune responses in BALB/c mice

Silva

Oliveira

Gouveia

et al. 2017

Clinical and Experimental Immunology

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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.

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“…Regarding the allergic diseases, obesity can affect lung function, in clinical asthma assessment and experimental models. In this context, obese asthmatics display a peculiar phenotype, with an immune response shift, usually associated with worsening of symptoms and resistance to conventional therapy . However, there is a lack of studies involving the EoE‐obesity association.…”

Section: Introductionmentioning

confidence: 99%

High‐fat diet‐induced obesity worsens TH2 immune response and immunopathologic characteristics in murine model of eosinophilic oesophagitis

Silva

Oliveira

Ambrósio

et al. 2019

Clin Experimental Allergy

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Background: Eosinophilic oesophagitis (EoE) is an emergent chronic immunemediated disease of the oesophagus, which affects both children and adults. It is clinically characterized by dysphagia, food impaction and oesophageal eosinophilia.Epidemiological studies indicate that obesity can worsen allergic symptoms; however, its effect on EoE immunopathological response has not been evaluated yet. This study aimed to assess the effect of obesity on allergic inflammation and T helper-2 profile in an EoE experimental model. Methods:Obesity was induced by high-fat feeding. After 7 weeks of diet, male BALB/c mice were subcutaneously sensitized and orally challenged with OVA.Results: Obesity itself induced a significant mast cell and eosinophil accumulation in the oesophagus, trachea, gut and lung. After allergy induction, this number was higher, when compared to lean-allergic mice. Moreover, obese-allergic mice showed higher remodelling area, in the oesophagus, associated with higher IL-5 and TSLP mRNA expression.In contrast, FoxP3 and IL-10 were less expressed in comparison with lean-allergic mice.In addition, the amount of CD11c + MHCII + PDL1 + dendritic cells was reduced, while the number of CD11c + MHCII + CD80 + DCs and CD3 + CD4 + GATA 3 + IL-4 + cells was increased in obese-allergic mice in the spleen and lymph nodes when compared to lean-allergic mice. Conclusion:Obesity aggravated the immune histopathological characteristics in the EoE experimental model, which was associated with the reduction in the regulatory profile, and the increased inflammatory cells influx, related to the T H 2 profile.Altogether, the data provide new knowledge about obesity as a risk factor, worsening EoE symptoms, and contribute for future treatment strategies for this specific profile. K E Y W O R D Sallergy, eosinophilic oesophagitis, immune response, inflammation, obesity | 245 SILVA et AL.

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Obesity shifts house dust mite-induced airway cellular infiltration from eosinophils to macrophages: effects of glucocorticoid treatment

Cited by 28 publications

References 66 publications

Short‐term high‐fat diet feeding protects from the development of experimental allergic asthma in mice

Short‐term high‐fat diet feeding protects from the development of experimental allergic asthma in mice

Obesity promotes prolonged ovalbumin-induced airway inflammation modulating T helper type 1 (Th1), Th2 and Th17 immune responses in BALB/c mice

High‐fat diet‐induced obesity worsens TH2 immune response and immunopathologic characteristics in murine model of eosinophilic oesophagitis

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