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Metal allergens nickel and cobalt facilitate TLR4 homodimerization independently of MD2
Author(s) -
Raghavan Badrinarayanan,
Martin Stefan F,
Esser Philipp R,
Goebeler Matthias,
Schmidt Marc
Publication year - 2012
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2012.155
Subject(s) - nickel , cobalt , metal , chemistry , metallurgy , materials science
Development of contact allergy requires cooperation of adaptive and innate immunity. Ni 2+ 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 Co 2+ 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.