Complexity and complementarity of outer membrane protein A recognition by cellular and humoral innate immunity receptors

Pascale Jeannin; Barbara Bottazzi; Marina Sironi; Andrea Doni; Marco Rusnati; Marco Presta; Virginia Maina; Giovanni Magistrelli; Jean François Haeuw; Guillaume Hoeffel; Nathalie Thieblemont; Nathalie Corvaia; Cecilia Garlanda; Yves Delneste; Alberto Mantovani

doi:10.1016/j.immuni.2005.03.008

Complexity and complementarity of outer membrane protein A recognition by cellular and humoral innate immunity receptors

Immunity. 2005 May;22(5):551-60. doi: 10.1016/j.immuni.2005.03.008.

Authors

Pascale Jeannin¹, Barbara Bottazzi, Marina Sironi, Andrea Doni, Marco Rusnati, Marco Presta, Virginia Maina, Giovanni Magistrelli, Jean François Haeuw, Guillaume Hoeffel, Nathalie Thieblemont, Nathalie Corvaia, Cecilia Garlanda, Yves Delneste, Alberto Mantovani

Affiliation

¹ Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon III, 74164 Saint-Julien en Genevois, France.

PMID: 15894273
DOI: 10.1016/j.immuni.2005.03.008

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bacterial Outer Membrane Proteins / immunology*
C-Reactive Protein / deficiency
C-Reactive Protein / genetics
C-Reactive Protein / immunology
C-Reactive Protein / metabolism
CHO Cells
Cricetinae
Dendritic Cells / immunology
Humans
Immunity, Cellular
Immunity, Innate
In Vitro Techniques
Klebsiella pneumoniae / immunology
Macrophage Activation
Mice
Mice, Inbred C57BL
Mice, Knockout
Models, Immunological
Nerve Tissue Proteins / deficiency
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / immunology
Nerve Tissue Proteins / metabolism
Receptors, Immunologic / deficiency
Receptors, Immunologic / genetics
Receptors, Immunologic / immunology
Receptors, Immunologic / metabolism*
Receptors, LDL / genetics
Receptors, LDL / immunology
Receptors, LDL / metabolism
Receptors, Oxidized LDL
Receptors, Scavenger
Recombinant Proteins / genetics
Recombinant Proteins / immunology
Recombinant Proteins / metabolism
Scavenger Receptors, Class E
Scavenger Receptors, Class F
Signal Transduction
Toll-Like Receptor 2
Transfection

Substances

Bacterial Outer Membrane Proteins
Nerve Tissue Proteins
OLR1 protein, human
Olr1 protein, mouse
Receptors, Immunologic
Receptors, LDL
Receptors, Oxidized LDL
Receptors, Scavenger
Recombinant Proteins
SCARF1 protein, human
Scavenger Receptors, Class E
Scavenger Receptors, Class F
Tlr2 protein, mouse
Toll-Like Receptor 2
neuronal pentraxin
OMPA outer membrane proteins
C-Reactive Protein