Circulating and airway neutrophils in cystic fibrosis display different TLR expression and responsiveness to interleukin-10.
We compared blood neutrophils (PMNs) collected from healthy subjects with PMNs derived from either blood or airways collected from the same cystic fibrosis (CF) patients. When compared to healthy blood PMNs, CF blood PMNs expressed enhanced level of CD64, a marker of neutrophil activation, and lower level of Toll-like receptor-2 (TLR2). CF airway PMNs expressed enhanced level of TLR4. Interleukin-8 (IL-8) production by CF blood PMNs could be enhanced upon addition of lipopolysaccharide or peptidoglycan, and this production was inhibited by recombinant human IL-10. In contrast, CF airway PMNs released spontaneously high level of IL-8 that was neither further enhanced by microbial activators nor inhibited by recombinant human IL-10. The levels of IL-10 receptors were similar in all types of neutrophils. These data further demonstrate that circulating PMNs from CF patients display a distinct pattern of surface markers, including TLRs, as compared to PMNs from healthy donors, and that airways PMNs from CF patients are primed and resistant to anti-inflammatory signals delivered by IL-10.
Unit Cytokines & Inflammation, Institut Pasteur, 28 rue Dr Roux, 75015 Paris, France.
Anne-France
AF
Petit-Bertron
Olivier
O
Tabary
Harriet
H
Corvol
Jacky
J
Jacquot
Annick
A
Clément
Jean-Marc
JM
Cavaillon
Minou
M
Adib-Conquy
D000293:Adolescent; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D002648:Child; D003550:Cystic Fibrosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects* / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D010457:Peptidoglycan / Q000494:pharmacology; D017452:Receptors, IgG / Q000096:biosynthesis / Q000276:immunology; D012137:Respiratory System / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000276:immunology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; C508609:IL10 protein, human; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D017452:Receptors, IgG; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016753:Interleukin-10