GP96 Drives Exacerbation of Secondary Bacterial Pneumonia following Influenza A Virus Infection
Tomoko Sumitomo, Masanobu Nakata, Satoshi Nagase, Yuki Takahara, Mariko Honda-Ogawa, Yasushi Mori, Yukako Akamatsu, M. Yamaguchi, Shigefumi Okamoto, Shigetada Kawabata
Abstract
Secondary bacterial pneumonia following an influenza A virus (IAV) infection is a major cause of morbidity and mortality. Although it is generally accepted that preceding IAV infection leads to increased susceptibility to secondary bacterial infection, details regarding the pathogenic mechanism during the early stage of superinfection remain elusive. Here, we focused on the interaction of IAV-infected cells and Streptococcus pneumoniae, which revealed that human epithelial cells infected with IAV exhibit a cell surface display of GP96, an endoplasmic reticulum chaperon. Notably, extracellular GP96 was shown to impart efficient adherence for secondary infection by S. pneumoniae, and GP96 inhibition ameliorated lung pathology of superinfected mice, indicating it to be a useful target for development of therapeutic strategies for patients with superinfection.