Outer membrane protein A (OmpA) is a conserved major component of the outer membrane of Enterobacteriaceae. Here, we report that OmpA from Klebsiella pneumoniae (KpOmpA) activates macrophages and dendritic cells (DCs) in a TLR2-dependent way. However, TLR2 does not account for binding of KpOmpA to innate immune cells. KpOmpA binds the scavenger receptors (SRs) LOX-1 and SREC-I, but not other members of the same family. LOX-1 colocalizes and cooperates with TLR2 in triggering cellular responses. The TLR2-activated functional program includes production of the long pentraxin PTX3, a soluble pattern recognition receptor involved in resistance against diverse pathogens. PTX3, in turn, binds KpOmpA but does not affect recognition of this microbial moiety by cellular receptors. KpOmpA-elicited in vivo inflammation is abrogated in TLR2(-/-) mice and significantly reduced in PTX3(-/-) mice. Thus, SR-mediated KpOmpA recognition and TLR2-dependent cellular activation set in motion a nonredundant PTX3-mediated humoral amplification loop of innate immunity.
|Titolo:||Complexity and complementarity of outer membrane protein A recognition by cellular and humoral innate immunity receptors|
MANTOVANI, ALBERTO (Ultimo)
|Parole Chiave:||Klebsiella pneumoniae ; analytic method ; article ; binding affinity ; cellular immunity ; dendritic cell ; gene targeting ; genetic transfection ; human ; humoral immunity ; in vivo study ; innate immunity ; macrophages ; nonhuman ; pattern recognition ; priority journal ; protein binding ; protein function ; protein localization ; signal transduction ; outer membrane protein ; scavenger receptors ; C-reactive protein ; acute phase protein ; long pentraxin PTX3 ; amyloid-P component ; toll-like receptors ; dendritic cells ; differentiation ; inflammation|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||17-mag-2005|
|Digital Object Identifier (DOI):||10.1016/j.immuni.2005.03.008|
|Appare nelle tipologie:||01 - Articolo su periodico|