Abstract
In cystic fibrosis (CF) infectious and allergic airway inflammation cause pulmonary exacerbations that destroy the lungs. Staphylococcus aureus is a common long-term colonizer and cause of recurrent airway infections in CF. The pathogen is also associated with respiratory allergy; especially the staphylococcal serine protease-like proteins (Spls) can induce type 2 immune responses in humans and mice. We measured the serum IgE levels specific to 7 proteases of S. aureus by ELISA, targeting 5 Spls (76 CF patients and 46 controls) and the staphopains A and B (16 CF patients and 46 controls). Then we compared cytokine release and phenotype of T cells that had been stimulated with Spls between 5 CF patients and 5 controls. CF patients had strongly increased serum IgE binding to all Spls but not to the staphopains. Compared to healthy controls, their Spl-stimulated T cells released more type 2 cytokines (IL-4, IL-5, IL-13) and more IL-6 with no difference in the secretion of type 1- or type 3 cytokines (IFNγ, IL-17A, IL-17F). IL-10 production was low in CF T cells. The phenotype of the Spl-exposed T cells shifted towards a Th2 or Th17 profile in CF but to a Th1 profile in controls. Sensitization to S. aureus Spls is common in CF. This discovery could explain episodes of allergic inflammation of hitherto unknown causation in CF and extend the diagnostic and therapeutic portfolio.
Highlights
Cystic fibrosis (CF) is the most common life-shortening genetic disorder, afflicting around 7/100 000 of the general population in the US and the European Union [1]
There was pronounced variability in the patterns of each patient’s IgE binding to the five serine protease-like proteins (Spls). This likely reflects the patients’ history of exposure to these enzymes: Spl-specific IgE tended to be higher in cystic fibrosis (CF) patients that were persistently colonized with S. aureus in the lung and in the nose; in the case of SplA this difference reached significance (Table 1)
While all Spls are encoded in one operon that is present in around 80% of clinical S. aureus isolates, the composition of this operon is variable, indicating that in S. aureus-infected CF patients the immune system is confronted with different subsets of the Spl proteins [16]
Summary
Cystic fibrosis (CF) is the most common life-shortening genetic disorder, afflicting around 7/100 000 of the general population in the US and the European Union [1]. Recurrent bacterial lung infection and persistent airway inflammation gradually destroy the lung, resulting in respiratory failure [2]. Persistent colonization with S. aureus occurs early in the disease course in up to 70% of CF patients, a much higher percentage than in the general population [2, 4]. The pathogen adapts to the host, gradually reducing its virulence during airway infection [5]. Recurrent pulmonary exacerbations gradually worsen the lung function and clinical condition of CF patients [6]
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