Stronger Toll-like receptor 1/2, 4, and 7/8 but less 9 responses in peripheral blood mononuclear cells in non-infectious exacerbated asthmatic children.
Toll-like receptors (TLR) initiate innate and often affect adaptive immune response. This study aimed to determine if TLR response and T regulatory cell (Treg) function in peripheral blood mononuclear cells (PBMC) correlate with clinical severity in non-infectious asthma. TLR1-9 expression and representative response cytokine TNF-α, IL-6, and IFN-β secretions were analyzed after stimulation by TLR1-9 ligands from 17 non-infectious asthmatic children. TNF-α production was higher in TLR1/2 (median 385.4 vs. 250.3 pg/ml in 1 μg/ml Pam3CSK4, p=0.0078), TLR4 (2392.4 vs. 1355.9 in 1 μg/ml LPS; p=0.0005), and TLR7/8 (10,776.2 vs. 4237.0 pg/ml in 1 μg/ml R848, p=0.0079) of patients in exacerbation than those in convalescence and healthy controls despite equal TLR expression. TNF-α production stimulated by TLR9 agonist was significantly lower in exacerbation (17.7 vs. 34.9 pg/ml in 1 μg/ml ODN2216, p=0.0175), while IL-6 production had similar patterns but was significantly lower in TLR3 signaling (119.7 vs. 245.0 pg/ml in 0.1 μg/ml poly(I:C), p=0.0033). IFN-β production by TLR3 agonist also decreased in exacerbation but not statistically significant. Six older children showed decreased FOXP3 percentage in CD4+CD25(high) and decreased suppression capability in exacerbation but restored in stabilization (82.8% vs. 90.0%, p=0.0061 and 60.9% vs. 81.7%, p=0.0071; respectively). In conclusion, normalizing imbalanced TLR signaling and enhancing Treg cell capability may guide possible therapeutic strategies for non-infectious asthma in exacerbation.
Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
Wen-I
WI
Lee
Tsung-Chieh
TC
Yao
Kuo-Wei
KW
Yeh
Li-Chen
LC
Chen
Liang-Shiou
LS
Ou
Jing-Long
JL
Huang
D056704:Adaptive Immunity; D001249:Asthma / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D002648:Child; D016207:Cytokines / Q000276:immunology*; D018450:Disease Progression; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D055666:Lipopeptides / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D051194:Toll-Like Receptor 1 / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000276:immunology; D051200:Toll-Like Receptor 8 / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology*
D016207:Cytokines; D007093:Imidazoles; D055666:Lipopeptides; D008070:Lipopolysaccharides; C508075:Pam(3)CSK(4) peptide; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9; C402365:resiquimod