Open AccessBacterial Outer Membrane Vesicles Provide Broad-Spectrum Protection against Influenza Virus Infection via Recruitment and Activation of Macrophages
Author(s) -
Bae Eun-Hye,
Seo Sang Hwan,
Kim Chang-Ung,
Jang Min Seong,
Song Min-Suk,
Lee Tae-Young,
Jeong Yu-Jin,
Lee Moo-Seung,
Park Jong-Hwan,
Lee Pureum,
Kim Young Sang,
Kim Sang-Hyun,
Kim Doo-Jin
Publication year - 2019
Publication title -
journal of innate immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.078
H-Index - 64
eISSN - 1662-8128
pISSN - 1662-811X
DOI - 10.1159/000494098
Subject(s) - research article
Influenza A virus (IAV) poses a constant worldwide threat to human health. Although conventional vaccines are available, their protective efficacy is type or strain specific, and their production is time-consuming. For the control of an influenza pandemic in particular, agents that are immediately effective against a wide range of virus variants should be developed. Although pretreatment of various Toll-like receptor (TLR) ligands have already been reported to be effective in the defense against subsequent IAV infection, the efficacy was limited to specific subtypes, and safety concerns were also raised. In this study, we investigated the protective effect of an attenuated bacterial outer membrane vesicle harboring modified lipid A moiety of lipopolysaccharide (fmOMV) against IAV infection and the underlying mechanisms. Administration of fmOMV conferred significant protection against a lethal dose of pandemic H1N1, PR8, H5N2, and highly pathogenic H5N1 viruses; this broad antiviral activity was dependent on macrophages but independent of neutrophils. fmOMV induced recruitment and activation of macrophages and elicited type I IFNs. Intriguingly, fmOMV showed a more significant protective effect than other TLR ligands tested in previous reports, without exhibiting any adverse effect. These results show the potential of fmOMV as a prophylactic agent for the defense against influenza virus infection.