Open AccessOX 40 ligand newly expressed on bronchiolar progenitors mediates influenza infection and further exacerbates pneumonia
Author(s) -
Hirano Taizou,
Kikuchi Toshiaki,
Tode Naoki,
Santoso Arif,
Yamada Mitsuhiro,
Mitsuhashi Yoshiya,
Komatsu Riyo,
Kawabe Takeshi,
Tanimoto Takeshi,
Ishii Naoto,
Tanaka Yuetsu,
Nishimura Hidekazu,
Nukiwa Toshihiro,
Watanabe Akira,
Ichinose Masakazu
Publication year - 2016
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201506154
Subject(s) - respiratory medicine , medicine , respiratory infection , medical school , library science , respiratory system , family medicine , medical education , surgery , computer science
Influenza virus epidemics potentially cause pneumonia, which is responsible for much of the mortality due to the excessive immune responses. The role of costimulatory OX 40– OX 40 ligand ( OX 40L) interactions has been explored in the non‐infectious pathology of influenza pneumonia. Here, we describe a critical contribution of OX 40L to infectious pathology, with OX 40L deficiency, but not OX 40 deficiency, resulting in decreased susceptibility to influenza viral infection. Upon infection, bronchiolar progenitors increase in number for repairing the influenza‐damaged epithelia. The OX 40L expression is induced on the progenitors for the antiviral immunity during the infectious process. However, these defense‐like host responses lead to more extensive infection owing to the induced OX 40L with α‐2,6 sialic acid modification, which augments the interaction with the viral hemagglutinin. In fact, the specific antibody against the sialylated site of OX 40L exhibited therapeutic potency in mitigating the OX 40L‐mediated susceptibility to influenza. Our data illustrate that the influenza‐induced expression of OX 40L on bronchiolar progenitors has pathogenic value to develop a novel therapeutic approach against influenza.