Obesity Enhances Non-Th2 Airway Inflammation in a Murine Model of Allergic Asthma

Int J Mol Sci. 2024 Jun 4;25(11):6170. doi: 10.3390/ijms25116170.

Abstract

Obese patients with asthma present with aggravated symptoms that are also harder to treat. Here, we used a mouse model of allergic asthma sensitised and challenged to house dust mite (HDM) extracts to determine whether high-fat-diet consumption would exacerbate the key features of allergic airway inflammation. C57BL/6 mice were intranasally sensitised and challenged with HDM extracts over a duration of 3 weeks. The impact of high-fat-diet (HFD) vs. normal diet (ND) chow was studied on HDM-induced lung inflammation and inflammatory cell infiltration as well as cytokine production. HFD-fed mice had greater inflammatory cell infiltration around airways and blood vessels, and an overall more severe degree of inflammation than in the ND-fed mice (semiquantitative blinded evaluation). Quantitative assessment of HDM-associated Th2 responses (numbers of lung CD4+ T cells, eosinophils, serum levels of allergen-specific IgE as well as the expression of Th2 cytokines (Il5 and Il13)) did not show significant changes between the HFD and ND groups. Interestingly, the HFD group exhibited a more pronounced neutrophilic infiltration within their lung tissues and an increase in non-Th2 cytokines (Il17, Tnfa, Tgf-b, Il-1b). These findings provide additional evidence that obesity triggered by a high-fat-diet regimen may exacerbate asthma by involving non-Th2 and neutrophilic pathways.

Keywords: airway inflammation; asthma; house dust mite; obesity.

MeSH terms

  • Allergens / immunology
  • Animals
  • Asthma* / etiology
  • Asthma* / immunology
  • Asthma* / metabolism
  • Asthma* / pathology
  • Cytokines* / metabolism
  • Diet, High-Fat* / adverse effects
  • Disease Models, Animal*
  • Female
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL*
  • Obesity* / immunology
  • Obesity* / metabolism
  • Pyroglyphidae / immunology
  • Th2 Cells* / immunology
  • Th2 Cells* / metabolism

Substances

  • Cytokines
  • Immunoglobulin E
  • Allergens