Impaired interleukin-8 chemokine secretion by staphylococcus aureus-activated epithelium and T-cell chemotaxis in cystic fibrosis.
Staphylococcus aureus is frequently isolated from lungs of patients with cystic fibrosis (CF). Upon lung infection with S. aureus, airway epithelial cells (AEC) produce high levels of chemokines that enhance T-cell chemotaxis. Although the number of lymphocytes is increased in the airways and bronchoalveolar lavage fluid of patients with CF, the mechanisms responsible for their accumulation and the role of S. aureus in this process are largely unknown. This study investigated early S. aureus impact on chemokine secretion by CF epithelial cells and chemotaxis of CF T cells. CF and non-CF AEC were grown in a cell culture model and apically stimulated with S. aureus. Supernatants were quantified for chemokine secretions and assayed for T-cell chemotaxis. CF AEC secreted constitutively larger amounts of IL-8, GROalpha, MIG, MIP-3beta, and MCP-1 than non-CF epithelial cells. S. aureus interaction with epithelial cells increased chemokine production by non-CF cells but had no effect on CF cells. Chemotaxis of T cells derived from patients with CF was greater than that of T cells from subjects without CF. Moreover, there were more CF T cells expressing CXCR1 as compared with non-CF T cells. Under our experimental conditions, inhibition of IL-8 or its receptor CXCR1 resulted in a considerable decrease in T-cell chemotaxis (up to 80%). These data suggest that IL-8 and its receptor CXCR1 are key players in the chemotaxis of CF T cells and could be used as targets to develop therapies for CF.
Al Alam
Denise
D
Laboratoire d'Immunologie et de Microbiologie EA3796, IFR53, UFR de Pharmacie 1 avenue du Maréchal Juin 51100 Reims, France.
Deslee
Gaetan
G
Tournois
Claire
C
Lamkhioued
Bouchaib
B
Lebargy
François
F
Merten
Marc
M
Belaaouaj
Azzaq
A
Guenounou
Moncef
M
Gangloff
Sophie Catherine
SC
D000328:Adult; D000911:Antibodies, Monoclonal; D017252:CD3 Complex / Q000276:immunology; D016022:Case-Control Studies; D002460:Cell Line; D002634:Chemotaxis, Leukocyte; D003550:Cystic Fibrosis / Q000276:immunology* / Q000382:microbiology; D017097:Electric Impedance; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology* / Q000378:metabolism; D008297:Male; D023062:Receptors, Interleukin-8A / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D013997:Time Factors; D055815:Young Adult
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; C508606:CXCL8 protein, human; D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins