Abstract
Obesity is associated with compartmentalized changes in immune responses that can be protective or pathogenic. It has been proposed that obesity-related changes in the microbiota influence allergic lung inflammation. We hypothesized that sensors of the bacterial cell wall influenced allergenic lung inflammation during obesity. Ovalbumin (OVA)-induced lung inflammation was similar in female Nod1-/- and wild-type mice during high-fat-diet-induced obesity, but allergic lung inflammation was higher in obese, high-fat-diet-fed female Nod2-/- mice. Obese Nod2-/- mice had higher inflammatory cell infiltration in the bronchial alveolar lavage (BAL) and lungs, pulmonary fibrosis, mucus levels, hypertrophy and hyperplasia of goblet cells, M2 alveolar macrophage infiltration, interleukin-4 (IL-4), IL-5, IL-6, and lower CXCL1 and IL-22. Therefore, Nod2 protects against excessive lung inflammation and is a bacterial sensor that relays protective responses to allergenic lung inflammation in obese female mice.