The IL-33/ST2 axis is crucial in type 2 airway responses induced by Staphylococcus aureus –derived serine protease–like protein D

Abstract

The S aureus-derived protein SplD is a potent allergen of S aureus and induces a T2-biased inflammatory response in the airways in an IL-33-dependent but TRL4-independent manner. The soluble ST2 receptor could be an efficient strategy to interfere with SplD-induced T2 inflammation but does not prevent the allergic sensitization.

Interleukin‐33 (IL‐33): A nuclear cytokine from the IL‐1 family

“…145,146 High amounts of sST2 are present in the serum of patients with various inflammatory diseases, and often correlate with disease severity. 144,145 Soluble sST2 can neutralize IL-33 in biological fluids 121,144,147 and high levels of sST2 may thus significantly inhibit IL-33 activity in vivo.…”

IL‐33 signalling contributes to pollutant‐induced allergic airway inflammation

“…This r-sST2 showed neutralizing activity towards murine IL-33 in a biological assay measuring IL-33-induced NF-κB receptor activation in ST2+IL1RAcP-transfected HEK293T cells. 33 For the therapeutic approach, mice were treated with PBS or 25 μg r-sST2 in PBS on days 14, 15 and 16 ( Figure 4A). The r-sST2 instillation was performed 8 min, previously optimized and published by our co-authors, after the exposure to saline, DEP, HDM or DEP+HDM ( Figure 2A).…”

“…33 Furthermore, an i.p. In a model of SplD-induced asthma, however, intratracheal administration of r-sST2 also minimally affected the inflammatory responses in the lung tissue.…”

“…The r-sST2 instillation was performed 8 min, previously optimized and published by our co-authors, after the exposure to saline, DEP, HDM or DEP+HDM ( Figure 2A). 33 For the therapeutic approach, mice were treated with PBS or 25 μg r-sST2 in PBS on days 14, 15 and 16 ( Figure 4A).…”

Allergy—A New Role for T Cell Superantigens of Staphylococcus aureus?

“…Furthermore, in the upper airways, S. aureus may grow intramucosally and even reside intracellularly [68,69]. S. aureus cells within nasal polyp tissue release numerous toxins and immune evasion molecules into the local environment, including SAgs but also staphylococcal serine protease-like (Spl) proteins, which are also suspected to play a role in allergies [26,70,71]. When the bacterium comes in contact with the immune system, specific IgG antibodies are formed against different bacterial components.…”