To cite this article: Foreman A., Holtappels G., Psaltis A.J., Jervis-Bardy J., Field J., Wormald P.-J., Bachert C. Adaptive immune responses in Staphylococcus aureus biofilm–associated chronic rhinosinusitis. Allergy 2011; 66: 1449–1456. Abstract Background: The etiopathogenesis of chronic rhinosinusitis (CRS) is currently an area of intense debate. Recently, biofilms have been proposed as a potential environmental trigger in this disease. In particular, Staphylococcus aureus biofilms appear to be a predictor of severe disease recalcitrant to current treatment paradigms. However, direct causal links between biofilms and host immune activation are currently lacking. This study aimed to document both the adaptive immune responses that characterize S. aureus biofilm–associated CRS and the relative contributions of staphylococcal superantigens and S. aureus biofilms in the inflammatory make-up of this disease. Methods: A total of 53 disease subjects and 15 controls were recruited. Sinonasal mucosa was collected for the determination of S. aureus and Haemophilus influenzae biofilms and presence of total and superantigen-specific IgE and for the measurement of cytokines that characterize the T-helper pathways. Results: Staphylococcus aureus biofilms and superantigens are significantly associated in CRS patients, suggesting the biofilm may be a nidus for superantigen-eluting bacteria. The presence of S. aureus biofilms is associated with eosinophilic inflammation, across the spectrum of CRS, on the back of a T-helper2 skewing of the host’s adaptive immune response (elevated Eosinophilic Cationic Protein and IL-5). This can be distinguished from the superantigenic effect resulting in the induction of IgE. Conclusion: This study provides novel evidence of a link between S. aureus biofilms and skewing of the T-cell response toward the T-helper2 pathway that is independent of superantigen activities. Further research is required to confirm the cause–effect relationship of this association.