Metal allergens nickel and cobalt facilitate TLR4 homodimerization independently of MD2
B Raghavan, SF Martin, PR Esser, M Goebeler… - EMBO …, 2012 - embopress.org
B Raghavan, SF Martin, PR Esser, M Goebeler, M Schmidt
EMBO reports, 2012•embopress.orgDevelopment of contact allergy requires cooperation of adaptive and innate immunity. Ni2+
stimulates innate immunity via TLR4/MD2, the bacterial LPS receptor. This likely involves
receptor dimerization, but direct proof is pending and it is unclear if related haptens share
this mechanism. We reveal Co2+ as second metal stimulating TLR4 and confirm necessity of
H456/H458 therein. Experiments with a new TLR4 dimerization mutant established
dimerization as a mechanism of metal‐and LPS‐induced TLR4 activation. Yet, in interaction …
stimulates innate immunity via TLR4/MD2, the bacterial LPS receptor. This likely involves
receptor dimerization, but direct proof is pending and it is unclear if related haptens share
this mechanism. We reveal Co2+ as second metal stimulating TLR4 and confirm necessity of
H456/H458 therein. Experiments with a new TLR4 dimerization mutant established
dimerization as a mechanism of metal‐and LPS‐induced TLR4 activation. Yet, in interaction …
Development of contact allergy requires cooperation of adaptive and innate immunity. Ni2+ stimulates innate immunity via TLR4/MD2, the bacterial LPS receptor. This likely involves receptor dimerization, but direct proof is pending and it is unclear if related haptens share this mechanism. We reveal Co2+ as second metal stimulating TLR4 and confirm necessity of H456/H458 therein. Experiments with a new TLR4 dimerization mutant established dimerization as a mechanism of metal‐ and LPS‐induced TLR4 activation. Yet, in interaction studies only LPS‐ but not metal‐induced dimerization required MD2. Consistently, soluble TLR4 expressed without MD2 inhibited metal‐ but not LPS‐induced responses, opening new therapeutic perspectives.
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