Enhanced Programmed Cell Death Protein 1/Programmed Cell Death Ligand 1 Expression Induced by Severe Influenza A...

Emerging research shows that the Programmed Cell Death Protein 1/Programmed Cell Death Ligand 1(PD-1/PD-L1) pathway modulates the antiviral response following influenza A virus (IAV) infection, and there is a need to understand further the role of the PD-1/PD-L1 signaling pathway in IAV infection. BALB/c mice were infected with different types of IAV to establish models of varying degrees of infection (mild and severe). The mice were pretreated with or without a PD-1 antagonist to evaluate the role of the PD-1/PD-L1 pathway in IAV infection. The general activity, degree of weight change, viral titer, pathological damage, protein expression, transcriptome level, and cytokine expression were evaluated in the mice. IAV infection, especially severe infection, induced expression of PD-1 and PD-L1 in the lungs and spleen of the mice at 6 days postinfection. Moreover, the expression level was positively correlated with the degree of pathological damage in the lung. PD-1 antagonists can alleviate weight loss in severely infected mice, reduce the viral load and pathological damage, enhance immune response-related gene expression, and induce the most robust responses of interferon-gamma without inducing an obvious Th1/Th17 response. The PD-1/PD-L1 signaling pathway induced by severe IAV infection seriously impairs the host's antiviral response; thus, blocking this signaling pathway may promote IAV recovery.