Staphylococcal enterotoxin B-derived haptens promote sensitization

Abstract

T helper 2 (Th2) polarization is a major pathological feature in allergic diseases; its etiology is not fully understood. This study aims to elucidate the adjuvant effect of the microbial product-derived small peptides in the initiation of antigen-specific Th2 polarization. In this study, a clinical survey of patients with chronic rhinosinusitis (CRS) and food allergy (FA) was carried out. The Staphylococcal enterotoxin B (SEB)-derived small peptides (Ssps) were examined in the human stool extracts. The formation of Ssp/antigen adducts was tested in a protein-protein combination assay. The bone marrow-derived dendritic cells (BMDCs) were employed to test the role of Ssp/ovalbumin (OVA) adducts in the dendritic cell (DC) maturation. A mouse model was developed to test the role of Ssp/OVA adducts in the initiation of Th2 polarization in the intestine. The results showed that 54 (18.2%) patients with FA were diagnosed among 296 patients with SEB 1 CRS; only eight (2.9%) FA patients were identified among 272 patients with SEB 2 CRS. Ssps were detected in the stool protein extracts from FA patients with SEB 1 CRS, but not in those with SEB 2 CRS. Ssp/OVA adducts induced DC maturation, speeded up DC migration, activated CD4 1 T cells in the regional lymph nodes and induced skewed Th2 polarization in the local tissue. We conclude that patients with SEB 1 CRS are prone to suffering from FA. SEB can be degraded to Ssps in the gastrointestinal tract. The Ssps can bind macromolecular antigens to form adducts to promote the antigenicity of the antigens and induction of the antigen-specific Th2 polarization and inflammation in the local tissue.

Forkhead box protein‐3 (Foxp3)‐producing dendritic cells suppress allergic response

“…The present data have expanded the previous findings by showing that SEB induced the expression of Foxp3 or STAT6 in DCs, depending on the concentrations of SEB in the micro‐environment. Our previous work also indicates that the components of SEB serve as a hapten or induce TIM4 expression to promote the development of intestinal allergy.…”

“…Staphylococcal enterotoxin B is one of the enterotoxins of S. aureus . S. aureus is a common bacterium distributing extensively on the surface of the body as well as in the airway and the digestive tract . In healthy conditions, the epithelial barrier prevents the products of S. aureus , such as SEB, from being absorbed.…”

Inhibition of squamous cancer growth in a mouse model by Staphylococcal enterotoxin B-triggered Th9 cell expansion

“…14 We have also found that SEB is decomposed into small peptides in the digestive tracts of patients with food allergies, and then the SEB peptides act as haptens, facilitating the development of food allergies. 15 These studies suggest that the use of SEB as an adjuvant may evoke a severe allergic reaction. To avoid a possible adverse reaction and maintain the immune system to ensure the efficacy of the immunotherapy, we reduced the dose of SEB from 10 mg/mouse in the food allergy study 14 to 2 mg/ mouse in the present study.…”

Staphylococcal enterotoxin B suppresses Alix and compromises intestinal epithelial barrier functions

“…Our data indicate that the over expression of Alix also has the inhibitory effect on SEB-induced epithelial barrier dysfunction. Previous studies suggest that SEB facilitates the development of intestinal allergy via modulating dendritic cell properties or act as an adjuvant [ 4 , 20 ]. The present data provide novel information that SEB also compromises the transcellular antigen transport in the epithelial barrier.…”