Novel strategies for targeting innate immune responses to influenza.

Détails

Ressource 1Télécharger: 26813341_BIB_0694E43E4827.pdf (617.02 [Ko])
Etat: Public
Version: Author's accepted manuscript
Licence: Non spécifiée
ID Serval
serval:BIB_0694E43E4827
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Novel strategies for targeting innate immune responses to influenza.
Périodique
Mucosal immunology
Auteur(s)
Shirey K.A., Lai W., Patel M.C., Pletneva L.M., Pang C., Kurt-Jones E., Lipsky M., Roger T., Calandra T., Tracey K.J., Al-Abed Y., Bowie A.G., Fasano A., Dinarello C.A., Gusovsky F., Blanco J.C., Vogel S.N.
ISSN
1935-3456 (Electronic)
ISSN-L
1933-0219
Statut éditorial
Publié
Date de publication
09/2016
Peer-reviewed
Oui
Volume
9
Numéro
5
Pages
1173-1182
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
We previously reported that TLR4(-/-) mice are refractory to mouse-adapted A/PR/8/34 (PR8) influenza-induced lethality and that therapeutic administration of the TLR4 antagonist Eritoran blocked PR8-induced lethality and acute lung injury (ALI) when given starting 2 days post infection. Herein we extend these findings: anti-TLR4- or -TLR2-specific IgG therapy also conferred significant protection of wild-type (WT) mice from lethal PR8 infection. If treatment is initiated 3 h before PR8 infection and continued daily for 4 days, Eritoran failed to protect WT and TLR4(-/-) mice, implying that Eritoran must block a virus-induced, non-TLR4 signal that is required for protection. Mechanistically, we determined that (i) Eritoran blocks high-mobility group B1 (HMGB1)-mediated, TLR4-dependent signaling in vitro and circulating HMGB1 in vivo, and an HMGB1 inhibitor protects against PR8; (ii) Eritoran inhibits pulmonary lung edema associated with ALI; (iii) interleukin (IL)-1β contributes significantly to PR8-induced lethality, as evidenced by partial protection by IL-1 receptor antagonist (IL-1Ra) therapy. Synergistic protection against PR8-induced lethality was achieved when Eritoran and the antiviral drug oseltamivir were administered starting 4 days post infection. Eritoran treatment does not prevent development of an adaptive immune response to subsequent PR8 challenge. Overall, our data support the potential of a host-targeted therapeutic approach to influenza infection.

Pubmed
Open Access
Oui
Création de la notice
15/02/2016 11:06
Dernière modification de la notice
20/08/2019 12:28
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