• J. Infect. Dis. · Nov 2015

    Genetic Variation in TLR10, an Inhibitory Toll-Like Receptor, Influences Susceptibility to Complicated Skin and Skin Structure Infections.

    • Mark H T Stappers, Marije Oosting, Mihai Ioana, Peter Reimnitz, Johan W Mouton, Mihai G Netea, Inge C Gyssens, and Leo A B Joosten.
    • Department of Internal Medicine, Radboud University Medical Center Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen Hasselt University, Belgium.
    • J. Infect. Dis. 2015 Nov 1;212(9):1491-9.

    BackgroundToll-like receptors (TLRs) play a central role in the innate immune response to complicated skin and skin structure infections (cSSSIs), with TLR10 being the first family member known to have an inhibitory function. This study assessed the role of TLR10 in recognition of cSSSI-related pathogens and whether genetic variation in TLR10 influences susceptibility to cSSSIs.MethodsHuman peripheral blood mononuclear cells (PBMCs) preincubated with anti-TLR10 antibody and HEK-293 cells overexpressing TLRs were exposed to cSSSI pathogens, and cytokine secretion was determined by enzyme-linked immunosorbent assay. A total of 318 patients with cSSSI and 328 healthy controls were genotyped for 4 nonsynonymous single-nucleotide polymorphisms in TLR10, and functional consequences of the TLR10 SNPs were assessed via in vitro stimulation assays.ResultsPBMC stimulation with cSSSI pathogens in the presence of TLR10 neutralizing antibody significantly increased interleukin 6 secretion. Overexpression of TLR10 completely abrogated TLR2-induced interleukin 8 secretion by HEK-293 cells in response to cSSSI pathogens. Three polymorphisms in TLR10, I775L, I369L, and N241H, were associated with reduced susceptibility to cSSSIs. The presence of the TLR10 alleles 775L, 369L, or 241H increased interleukin 6 secretion by PBMCs in response to cSSSI pathogens.ConclusionsTLR10 is a modulatory receptor of innate immune responses to cSSSI-related pathogens, and genetic variants in TLR10 are associated with protection against cSSSIs.© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…