Nmp4-deficiency protects mice from influenza A virus infection

Abstract

Abstract Severe influenza A virus infection typically triggers excessive and detrimental lung inflammation with massive cell infiltration and hyper-production of cytokines and chemokines. Discovering research models to alleviate lung damage without compromising viral control is critical. Here we identify that the lack of transcription factor-nuclear matrix protein 4 (Nmp4) protects mice from acute influenza virus infection by modulating the early stage inflammation. Upon infection, Nmp4-deficient mice lose only 5% body weight compared to 20% for the wild type (WT) mice. Furthermore, Nmp4-deficiency significantly reduces the recruitment of neutrophils and macrophages in the bronchoalveolar lavage fluid and lung parenchyma. Consistent with the fewer innate cells in the airways, influenza infected Nmp4-deficient mice have significantly decreased expression of cytokines and chemokines, such as IL-1β, TNF, IFN-γ, and MCP-1. However, Nmp4-deficient mice show similar viral control and adaptive immune responses to the WT mice with comparable virus specific CD8 T cells, CD4 T cells and anti-viral antibodies. Taken together, our data suggest that loss of Nmp4 protects mice from immune-driven lung damage without affecting viral clearance and may serve as a therapeutic target for severe influenza infection.