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.
Jeannin
Pascale
P
Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon III, 74164 Saint-Julien en Genevois, France.
Bottazzi
Barbara
B
Sironi
Marina
M
Doni
Andrea
A
Rusnati
Marco
M
Presta
Marco
M
Maina
Virginia
V
Magistrelli
Giovanni
G
Haeuw
Jean François
JF
Hoeffel
Guillaume
G
Thieblemont
Nathalie
N
Corvaia
Nathalie
N
Garlanda
Cecilia
C
Delneste
Yves
Y
Mantovani
Alberto
A
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002097:C-Reactive Protein / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D066298:In Vitro Techniques; D007711:Klebsiella pneumoniae / Q000276:immunology; D008262:Macrophage Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018448:Models, Immunological; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051131:Receptors, Oxidized LDL; D051116:Receptors, Scavenger; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051127:Scavenger Receptors, Class E; D051128:Scavenger Receptors, Class F; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D014162:Transfection; D000099153:Pentraxins
D001425:Bacterial Outer Membrane Proteins; D002097:C-Reactive Protein; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; D051127:Scavenger Receptors, Class E; D051128:Scavenger Receptors, Class F; D051195:Toll-Like Receptor 2; D000099153:Pentraxins; C495137:OLR1 protein, human; C495138:Olr1 protein, mouse; C495126:SCARF1 protein, human; C493486:Tlr2 protein, mouse; C078167:OMPA outer membrane proteins