IL-10 controls Aspergillus fumigatus- and Pseudomonas aeruginosa-specific T-cell response in cystic fibrosis.
Up to 90% of patients with cystic fibrosis (CF) are chronically colonized with Pseudomonas aeruginosa, and 10% to 50% of CF patients are colonized with Aspergillus fumigatus. Despite an extensive inflammatory reaction, patients cannot eliminate the microorganisms. The present study demonstrates that an IL-10 mediated T-cell tolerance to major infectious agents A. fumigatus and P. aeruginosa plays an important role in the control of T-cell-mediated inflammatory responses in CF. Peripheral blood mononuclear cells of CF patients secreted significantly higher amounts of IL-10. T-cell response against recombinant A. fumigatus antigens rAsp f 3, rAsp f 4, rAsp f 6, and heat-inactivated P. aeruginosa was controlled by IL-10. Proliferation and interferon-gamma production was significantly increased when endogenous IL-10 was blocked in aspergillus and pseudomonas antigen-stimulated cells of CF patients. The role of IL-10 was further documented by increased spontaneous proliferation of peripheral blood mononuclear cells of CF patients after preincubation with antisense oligonucleotides blocking the synthesis of IL-10 receptor-associated kinases janus tyrosine kinase 1 and tyrosine kinase 2. Together, these data demonstrate an important role of IL-10-mediated peripheral T-cell tolerance to P. aeruginosa and A. fumigatus in the control of the intensity of the inflammatory T-cell response in CF.
Casaulta
Carmen
C
Department of Pediatrics, University Children's Hospital, Inselspital, Bern, Switzerland. carmen.casaulta@insel.ch
Schöni
Martin H
MH
Weichel
Michael
M
Crameri
Reto
R
Jutel
Marek
M
Daigle
Isabelle
I
Akdis
Mübeccel
M
Blaser
Kurt
K
Akdis
Cezmi A
CA
D000293:Adolescent; D000328:Adult; D001232:Aspergillus fumigatus / Q000276:immunology* / Q000302:isolation & purification; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D003550:Cystic Fibrosis / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D007111:Immunity, Cellular; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis / Q000502:physiology*; D053613:Janus Kinase 1; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology; D009894:Opportunistic Infections / Q000097:blood / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011506:Proteins / Q000502:physiology; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000302:isolation & purification; D018123:Receptors, Interleukin / Q000502:physiology; D053701:Receptors, Interleukin-10; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology*; D053634:TYK2 Kinase
D011506:Proteins; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D016753:Interleukin-10; D007073:Immunoglobulin E; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1; D053634:TYK2 Kinase; C070139:TYK2 protein, human