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Altered Toll-Like Receptor Signalling in Children with Down Syndrome
Joint Authors
Huggard, Dean
Koay, W. J.
Kelly, Lynne
McGrane, Fiona
Ryan, Emer
Lagan, Niamh
Roche, Edna
Balfe, Joanne
Leahy, T. Ronan
Franklin, Orla
Moreno-Oliveira, Ana
Melo, Ashanty M.
Molloy, Eleanor J.
Doherty, Derek G.
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-09-12
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Toll-like receptors (TLRs) are the key in initiating innate immune responses.
TLR2 is crucial in recognising lipopeptides from gram-positive bacteria and is implicated in chronic inflammation.
Children with Down syndrome (DS) are prone to infections from these pathogens and have an increased risk of autoimmunity.
Sparstolonin B (SsnB) is a TLR antagonist which attenuates cytokine production and improves outcomes in sepsis.
We hypothesised that TLR signalling may be abnormal in children with DS and contribute to their clinical phenotype.
We evaluated TLR pathways in 3 ways: determining the expression of TLR2 on the surface of neutrophils and monocytes by flow cytometry, examining the gene expression of key regulatory proteins involved in TLR signal propagation, MyD88, IRAK4, and TRIF, by quantitative PCR, and lastly determining the cytokine production by ELISA following immunomodulation with proinflammatory stimuli (lipopolysaccharide (LPS), Pam3Csk4) and the anti-inflammatory agent SsnB.
We report TLR2 expression being significantly increased on neutrophils, total monocytes, and intermediate and nonclassical monocytes in children with DS (n=20, mean age 8.8±SD 5.3 years, female n=11) compared to controls (n=15, mean age 6.2±4.2 years, female n=5).
At baseline, the expression of MyD88 was significantly lower, and TRIF significantly raised in children with DS.
The TLR antagonist SsnB was effective in reducing TLR2 and CD11b expression and abrogating cytokine production in both cohorts.
We conclude that TLR signalling and the TLR2 pathway are dysregulated in DS, and this disparate innate immunity may contribute to chronic inflammation in DS.
SsnB attenuates proinflammatory mediators and may be of therapeutic benefit.
American Psychological Association (APA)
Huggard, Dean& Koay, W. J.& Kelly, Lynne& McGrane, Fiona& Ryan, Emer& Lagan, Niamh…[et al.]. 2019. Altered Toll-Like Receptor Signalling in Children with Down Syndrome. Mediators of Inflammation،Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1192850
Modern Language Association (MLA)
Huggard, Dean…[et al.]. Altered Toll-Like Receptor Signalling in Children with Down Syndrome. Mediators of Inflammation No. 2019 (2019), pp.1-13.
https://search.emarefa.net/detail/BIM-1192850
American Medical Association (AMA)
Huggard, Dean& Koay, W. J.& Kelly, Lynne& McGrane, Fiona& Ryan, Emer& Lagan, Niamh…[et al.]. Altered Toll-Like Receptor Signalling in Children with Down Syndrome. Mediators of Inflammation. 2019. Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1192850
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1192850