Complexity and Complementarity of Outer Membrane Protein A Recognition by Cellular and Humoral Innate Immunity Receptors
Copyright policy )Complexity and Complementarity of Outer Membrane Protein A Recognition by Cellular and Humoral Innate Immunity Receptors
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.
Immunology, Nerve Tissue Proteins, CHO Cells, In Vitro Techniques, Mice, Cricetinae, Immunology and Allergy, Animals, Humans, Receptors, Immunologic, Mice, Knockout, Immunity, Cellular, Models, Immunological, Dendritic Cells, Macrophage Activation, Immunity, Innate, Mice, Inbred C57BL, Klebsiella pneumoniae, Receptors, Oxidized LDL, Infectious Diseases, C-Reactive Protein, Receptors, LDL, 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, Bacterial Outer Membrane Proteins
Immunology, Nerve Tissue Proteins, CHO Cells, In Vitro Techniques, Mice, Cricetinae, Immunology and Allergy, Animals, Humans, Receptors, Immunologic, Mice, Knockout, Immunity, Cellular, Models, Immunological, Dendritic Cells, Macrophage Activation, Immunity, Innate, Mice, Inbred C57BL, Klebsiella pneumoniae, Receptors, Oxidized LDL, Infectious Diseases, C-Reactive Protein, Receptors, LDL, 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, Bacterial Outer Membrane Proteins
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