Complement dependent amplification of the innate response to a cognate microbial ligand by the long pentraxin PTX3

Alessia Cotena, Virginia Maina, Marina Sironi, Barbara Bottazzi, Pascale Jeannin, Annunciata Vecchi, Nathalie Corvaia, Mohamed R. Daha, Alberto Mantovani, Cecilia Garlanda

Research output: Contribution to journalArticlepeer-review

Abstract

The long pentraxin PTX3 is a fluid-phase pattern recognition receptor, which plays a nonredundant role in resistance against selected pathogens. PTX3 has properties similar to Abs; its production is induced by pathogen recognition, it recognizes microbial moieties, activates complement, and facilitates cellular recognition by phagocytes. The mechanisms responsible for the effector function of PTX3 in vivo have not been elucidated. OmpA, a major outer membrane protein of Gram-negative Enterobacteriaceae, is a microbial moiety recognized by PTX3. In the air pouch model, KpOmpA induces an inflammatory response, which is amplified by coadministration of PTX3 in terms of leukocyte recruitment and proinflammatory cytokine production. PTX3 did not affect the inflammatory response to LPS, a microbial moiety not recognized by PTX3. As PTX3 binds to C1q and modulates the activation of the complement cascade, we assessed the involvement of complement in the amplification of the response elicited by KpOmpA and PTX3. Experiments performed using cobra venom factor, C1-esterase inhibitor, and soluble complement receptor 1 indicate that PTX3 amplifies the inflammatory response to KpOmpA through complement activation. The results reported here demonstrate that PTX3 activates a complement-dependent humoral amplification loop of the innate response to a microbial ligand.

Original languageEnglish
Pages (from-to)6311-6317
Number of pages7
JournalJournal of Immunology
Volume179
Issue number9
Publication statusPublished - Nov 1 2007

ASJC Scopus subject areas

  • Immunology

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