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-gamma-dependent effector pathway.

Pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation / S. Bozza, F. Bistoni, R. Gaziano, L. Pitzurra, T. Zelante, P. Bonifazi, K. Perruccio, S. Bellocchio, M. Neri, A.M. Iorio, G. Salvatori, R. De Santis, M. Calvitti, A. Doni, C. Garlanda, A. Mantovani , L. Romani. - In: BLOOD. - ISSN 0006-4971. - 108:10(2006 Nov 15), pp. 3387-3396.

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

A. Mantovani
Penultimo
;
2006

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-gamma-dependent effector pathway.
Settore MED/04 - Patologia Generale
15-nov-2006
http://bloodjournal.hematologylibrary.org/cgi/content/full/108/10/3387
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/27773
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