TY - JOUR
T1 - Recognition of coxiella burnetii by toll-like receptors and nucleotide-binding oligomerization domain-like receptors
AU - Ammerdorffer, Anne
AU - Schoffelen, Teske
AU - Gresnigt, Mark S.
AU - Oosting, Marije
AU - Den Brok, Martijn H.
AU - Abdollahi-Roodsaz, Shahla
AU - Kanneganti, Thirumala Devi
AU - De Jong, Dirk J.
AU - Van Deuren, Marcel
AU - Roest, Hendrik Jan
AU - Rebel, Johanna M.J.
AU - Netea, Mihai G.
AU - Joosten, Leo A.B.
AU - Sprong, Tom
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Coxiella burnetii
KW - innate immunity
KW - NOD-like receptors
KW - pattern recognition
KW - Q fever
KW - singlenucleotide polymorphism
KW - Toll-like receptors
U2 - 10.1093/infdis/jiu526
DO - 10.1093/infdis/jiu526
M3 - Article
C2 - 25246533
AN - SCOPUS:84924405867
SN - 0022-1899
VL - 211
SP - 978
EP - 987
JO - The Journal of Infectious Diseases
JF - The Journal of Infectious Diseases
IS - 6
ER -