NOD2 protects against allergic lung inflammation in obese female mice

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.