T cell inflammatory response, Foxp3 and TNFRS18-L regulation of peripheral blood mononuclear cells from patients with nasal polyps-asthma after staphylococcal superantigen stimulation.
BACKGROUND
Staphylococcal superantigens may modulate airway inflammatory disease.


OBJECTIVE
We assessed the effect of Staphylococcus aureus enterotoxin B (SEB) on T cell activation in patients with nasal polyps and asthma, and its possible link to aspirin hypersensitivity.


METHODS
Leucocytes were isolated from five healthy subjects (controls), five asthmatics with nasal polyps without (NP-ATA) and five with aspirin-induced asthma (NP-AIA). Cells were incubated with increasing concentrations of SEB for 4 and 18 h. Release of T(H)1/T(H)2 cytokines was assessed by Cytometric Bead-Array. Foxp3 and TNFRS18-L expression were analysed by qPCR and flow cytometry.


RESULTS
After 4 and 18 h, SEB significantly increased IFN-gamma, IL-4, TNF-alpha, IL-5 and IL-2 concentrations in supernatants of both NP polyp groups compared with controls. Baseline Foxp3 was significantly decreased in both NP-asthma groups. Incubation with SEB for 4 h induced a limited up-regulation of Foxp3 in NP-AIA patients, which was switched off consecutively. Foxp3 was significantly up-regulated in the control group after 18 h, but not in the NP-asthmatic groups. In parallel, TNFRS18-L mRNA significantly increased after 18 h in the NP-asthma groups compared with control subjects. This molecule was highly expressed in CD11c(+)CD14(+) cells and its levels increased after 18 and 24 h culture in the NP-asthma patients.


CONCLUSIONS
SEB induces both T(H)1 and T(H)2 pro-inflammatory responses in patients with nasal polyps and asthma regardless of the presence of aspirin hypersensitivity. The nature of this response may be linked to a basal deficiency of Foxp3 observed in the NP-asthmatic patients and/or to the up-regulation of TNFRS18-L on monocytes/dendritic cell precursors.
Pérez Novo
C A
CA
Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, De Pintelaan 185, Ghent, Belgium. Claudina.Pereznovo@UGent.be
Jedrzejczak-Czechowicz
M
M
Lewandowska-Polak
A
A
Claeys
C
C
Holtappels
G
G
Van Cauwenberge
P
P
Kowalski
M L
ML
Bachert
C
C
D000328:Adult; D000368:Aged; D055963:Asthma, Aspirin-Induced / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D007963:Leukocytes, Mononuclear; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000276:immunology*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D004768:Enterotoxins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053450:Glucocorticoid-Induced TNFR-Related Protein; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D018089:Superantigens; C491405:TNFRSF18 protein, human; C031818:enterotoxin B, staphylococcal