NOD2 Signaling Circuitry during Allergen Sensitization Does Not Worsen Experimental Neutrophilic Asthma but Promotes a Th2/Th17 Profile in Asthma Patients but Not Healthy Subjects

Abstract

Nucleotide-binding oligomerization domain 2 (NOD2) recognizes pathogens associated with the development of asthma. Moreover, NOD2 adjuvants are used in vaccine design to boost immune responses. Muramyl di-peptide (MDP) is a NOD2 ligand, which is able to promote Th2/Th17 responses. Furthermore, polymorphisms of the NOD2 receptor are associated with allergy and asthma development. This study aimed to evaluate if MDP given as an adjuvant during allergen sensitization may worsen the development of Th2/Th17 responses. We used a mouse model of Th2/Th17-type allergic neutrophil airway inflammation (AAI) to dog allergen, with in vitro polarization of human naive T cells by dendritic cells (DC) from healthy and dog-allergic asthma subjects. In the mouse model, intranasal co-administration of MDP did not modify the AAI parameters, including Th2/Th17-type lung inflammation. In humans, MDP co-stimulation of allergen-primed DC did not change the polarization profile of T cells in healthy subjects but elicited a Th2/Th17 profile in asthma subjects, as compared with MDP alone. These results support the idea that NOD2 may not be involved in the infection-related development of asthma and that, while care has to be taken in asthma patients, NOD2 adjuvants might be used in non-sensitized individuals.

The landscape of rare genetic variation associated with inflammatory bowel disease and Parkinson’s disease comorbidity

“…PheWAS results also revealed interesting pleiotropic effects of these genes, which have been shown to exert relevant functions in the identified phenotypes, such as the associations of NOD2 and hypercoagulability (286.81 and 286.8) [61] and asthma (495) [62], IL6ST and joint disease (727.4) [63] and systemic and cutaneous lupus erythematosus (695.4, 695.42, and 695.41) [64], and IFNAR1 and viral hepatitis [65]. Moreover, candidate genes displayed associations with various other autoimmune and allergic conditions, including ankylosing spondylitis, enthesopathy, rheumatoid arthritis, erythematous skin lesions, eosinophilia, and polyarteritis nodosa.…”

Editorial of Special Issue “Molecular Mechanisms of Allergy and Asthma 2.0”

“…Taking the origin of natural SCFAs in human organisms into account, this could stimulate the development of personalized nutritional therapeutic approaches against allergies, autoimmune, and other chronic inflammatory disorders. Bouté and colleagues [4] observed that the co-stimulation of nucleotide-binding oligomerization domain 2 (NOD2) with muramyl di-peptide (MDP) during allergen sensitization did not worsen Th2/Th17-type allergic airway inflammation in a mouse model; however, MDP co-stimulation of allergen-primed dendritic cells (DCs) promoted a Th2/Th17 profile in asthma patients but not in healthy subjects. Considering that NOD2 adjuvants are used in vaccine design to boost immune responses, whereas care needs to be taken in asthmatics, those might be used in non-sensitized individuals.…”