1. OX40 ligand newly expressed on bronchiolar progenitors mediates influenza infection and further exacerbates pneumonia.
- Author
-
Hirano T, Kikuchi T, Tode N, Santoso A, Yamada M, Mitsuhashi Y, Komatsu R, Kawabe T, Tanimoto T, Ishii N, Tanaka Y, Nishimura H, Nukiwa T, Watanabe A, and Ichinose M
- Subjects
- Animals, Disease Susceptibility, Mice, Inbred C57BL, OX40 Ligand chemistry, Orthomyxoviridae Infections virology, Pneumonia, Viral virology, Protein Processing, Post-Translational, Sialic Acids analysis, Stem Cells virology, Host-Pathogen Interactions, Influenza A virus physiology, OX40 Ligand metabolism, Orthomyxoviridae Infections pathology, Pneumonia, Viral pathology, Stem Cells metabolism, Virus Attachment
- Abstract
Influenza virus epidemics potentially cause pneumonia, which is responsible for much of the mortality due to the excessive immune responses. The role of costimulatory OX40-OX40 ligand (OX40L) interactions has been explored in the non-infectious pathology of influenza pneumonia. Here, we describe a critical contribution of OX40L to infectious pathology, with OX40L deficiency, but not OX40 deficiency, resulting in decreased susceptibility to influenza viral infection. Upon infection, bronchiolar progenitors increase in number for repairing the influenza-damaged epithelia. The OX40L 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 OX40L 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 OX40L exhibited therapeutic potency in mitigating the OX40L-mediated susceptibility to influenza. Our data illustrate that the influenza-induced expression of OX40L on bronchiolar progenitors has pathogenic value to develop a novel therapeutic approach against influenza., (© 2016 The Authors. Published under the terms of the CC BY 4.0 license.)
- Published
- 2016
- Full Text
- View/download PDF