Pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation

Silvia Bozza, Francesco Bistoni, Roberta Gaziano, Lucia Pitzurra, Teresa Zelante, Pierluigi Bonifazi, Katia Perruccio, Silvia Bellocchio, Mariella Neri, Anna Maria Iorio, Giovanni Salvatori, Rita De Santis, Mario Calvitti, Andrea Doni, Cecilia Garlanda, Alberto Mantovani, Luigina Romani

Research output: Contribution to journalArticle

Abstract

Reactivation of latent human cytomegalovirus (HCMV) following allogeneic transplantation is a major cause of morbidity and mortality and predisposes to severe complications, including superinfection by Aspergillus species (spp). Antimicrobial polypeptides, including defensins and mannan-binding lectin, are known to block viral fusion by cross-linking sugars on cell surface. Pentraxin 3 (PTX3), a member of the long pentraxin family, successfully restored antifungal immunity in experimental hematopoietic transplantation. We assessed here whether PTX3 binds HCMV and murine virus (MCMV) and the impact on viral infectivity and superinfection in vivo. We found that PTX3 bound both viruses, reduced viral entry and infectivity in vitro, and protected from MCMV primary infection and reactivation as well as Aspergillus superinfection. This occurred through the activation of interferon (IFN) regulatory factor 3 (IRF3) in dendritic cells via the TLR9/MyD88-independent viral recognition sensing and the promotion of the interleukin-12 (IL-12)/IFN-γ-dependent effector pathway.

Original languageEnglish
Pages (from-to)3387-3396
Number of pages10
JournalBlood
Volume108
Issue number10
DOIs
Publication statusPublished - Nov 15 2006

ASJC Scopus subject areas

  • Hematology

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    Bozza, S., Bistoni, F., Gaziano, R., Pitzurra, L., Zelante, T., Bonifazi, P., Perruccio, K., Bellocchio, S., Neri, M., Iorio, A. M., Salvatori, G., De Santis, R., Calvitti, M., Doni, A., Garlanda, C., Mantovani, A., & Romani, L. (2006). Pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation. Blood, 108(10), 3387-3396. https://doi.org/10.1182/blood-2006-03-009266