Recognition of coxiella burnetii by toll-like receptors and nucleotide-binding oligomerization domain-like receptors

Anne Ammerdorffer, Teske Schoffelen, Mark S. Gresnigt, Marije Oosting, Martijn H. Den Brok, Shahla Abdollahi-Roodsaz, Thirumala Devi Kanneganti, Dirk J. De Jong, Marcel Van Deuren, Hendrik Jan Roest, Johanna M.J. Rebel, Mihai G. Netea, Leo A.B. Joosten, Tom Sprong*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

Abstract

Background. Infection with Coxiella burnetii can lead to acute and chronic Q fever. Toll-like receptor 1 (TLR1), TLR2, TLR4, TLR6, nucleotide-binding oligomerization domain receptor 1 (NOD1), NOD2, and the mitogen-activated protein kinases are central in the innate immune response against microorganisms, but little is known about their role in the recognition of C. burnetii in humans. Methods. Human peripheral blood mononuclear cells (PBMCs) were stimulated with C. burnetii Nine Mile and the Dutch outbreak isolate C. burnetii 3262. TLRs were inhibited using specific antibodies or antagonists. Additionally, the influence of human polymorphisms in TLRs and Nod-like receptors (NLRs) on C. burnetii-induced cytokine production was assessed. Results. Inhibition of TLR2, p38, JNK, and ERK led to decreased cytokine responses in C. burnetii-stimulated human PBMCs. Humans with polymorphisms in TLR1 and NOD2 had reduced cytokine production, compared with humans with wild-type genotypes, after stimulation. Interestingly, polymorphisms in TLR6 led to decreased cytokine production after C. burnetii 3262 stimulation but not after C. burnetii Nine Mile stimulation. Conclusions. The TLR1/TLR2 heterodimer and NOD2 are important recognition receptors for the induction of cytokine responses against C. burnetii in humans. Furthermore, an interesting finding was the divergent recognition of C. burnetii Nine Mile and C. burnetii 3262.

Original languageEnglish
Pages (from-to)978-987
JournalThe Journal of Infectious Diseases
Volume211
Issue number6
DOIs
Publication statusPublished - 2015

Keywords

  • Coxiella burnetii
  • innate immunity
  • NOD-like receptors
  • pattern recognition
  • Q fever
  • singlenucleotide polymorphism
  • Toll-like receptors

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    Ammerdorffer, A., Schoffelen, T., Gresnigt, M. S., Oosting, M., Den Brok, M. H., Abdollahi-Roodsaz, S., Kanneganti, T. D., De Jong, D. J., Van Deuren, M., Roest, H. J., Rebel, J. M. J., Netea, M. G., Joosten, L. A. B., & Sprong, T. (2015). Recognition of coxiella burnetii by toll-like receptors and nucleotide-binding oligomerization domain-like receptors. The Journal of Infectious Diseases, 211(6), 978-987. https://doi.org/10.1093/infdis/jiu526