Role of staphylococcal superantigens in upper airway disease

Abstract

From this new understanding of chronic rhinosinusitis with nasal polyps, new therapeutic approaches emerge such as anti-interleukin-5, anti-immunoglobulin E, and antibiotic treatment. These may enlarge the nonsurgical armentarium.

Mepolizumab, a humanized anti–IL-5 mAb, as a treatment option for severe nasal polyposis

“…10 Concerning the increased IgE level, there is increasing evidence that Staphylococcus aureus-derived enterotoxins stimulate eosinophilic inflammation through production of T H 2 cytokines and local IgE formation. 13 Interestingly, NPs of Chinese patients are clinically indistinguishable from polyps of their white counterparts, but they lack IL-5 and eotaxin expression in the tissue, resulting in lower numbers of tissue eosinophils. 14,15 The direct comparison of polyps from Belgian and Chinese patients shows that there is a shared but still to be clarified pathway of mucosal edema formation, T-effector cell activation, and regulatory T-cell impairment.…”

Th2-associated immunity to bacteria in teenagers and susceptibility to asthma

“…Considerably less attention has been paid to bacteria, with the exception of Staphylococcus aureus (SA) strains which produce soluble enterotoxins. These molecules function as superantigens and can directly activate a large proportion of peripheral T-cells [4], triggering polyclonal production of both T-helper (Th)1 and Th2 cytokines and synthesis of enterotoxinspecific immunoglobulin (Ig)E. Colonisation with superantigen-producing SA has been suggested to play a role in a range of atopy-associated diseases, including atopic dermatitis [5], rhinosinusitis and allergic rhinitis [6,7], as well as adult asthma [8,9] and childhood wheeze [10]. Recently, colonisation of the upper airways during early childhood with bacterial pathogens, including nonenterotoxin-producing strains, has been linked with subsequent development of persistent asthma [11], but the pathogenic mechanisms are unknown and the interpretation of these findings remains controversial [12].…”

Molecular Requirements for MHC Class II α-Chain Engagement and Allelic Discrimination by the Bacterial Superantigen Streptococcal Pyrogenic Exotoxin C

“…The one critical residue from the HLA-DQ2␣3␤ analysis, Tyr 87 , which is also critical for engaging the HLA-DR isoforms, likely hydrogen bonds with the side chain from the invariant MHC␣ residue Lys 39 . Our model also predicts that the lower portions of the SpeC-HLA-DQ2␣3␤ interface would fit in a pocked formed between the MHC␣ ␤1-␤2 and ␤3-␤4 loops, potentially interacting with ␣Pro 18 /␣Ser 19 and ␣Leu 36 /␣Gly 37 /␣Arg 38 (Fig. 5E).…”