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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)551-560
Number of pages10
JournalImmunity
Volume22
Issue number5
DOIs
Publication statusPublished - May 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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    Jeannin, P., Bottazzi, B., Sironi, M., Doni, A., Rusnati, M., Presta, M., Maina, V., Magistrelli, G., Haeuw, J. F., Hoeffel, G., Thieblemont, N., Corvaia, N., Garlanda, C., Delneste, Y., & Mantovani, A. (2005). Complexity and complementarity of outer membrane protein A recognition by cellular and humoral innate immunity receptors. Immunity, 22(5), 551-560. https://doi.org/10.1016/j.immuni.2005.03.008