Host Immune Response to Influenza A Virus Infection

Abstract

Influenza A viruses (IAVs) are contagious pathogens responsible for severe respiratory infection in humans and animals worldwide. Upon detection of IAV infection, host immune system aims to defend against and clear the viral infection. Innate immune system is comprised of physical barriers (mucus and collectins), various phagocytic cells, group of cytokines, interferons (IFNs), and IFN-stimulated genes, which provide first line of defense against IAV infection. The adaptive immunity is mediated by B cells and T cells, characterized with antigen-specific memory cells, capturing and neutralizing the pathogen. The humoral immune response functions through hemagglutinin-specific circulating antibodies to neutralize IAV. In addition, antibodies can bind to the surface of infected cells and induce antibody-dependent cell-mediated cytotoxicity or complement activation. Although there are neutralizing antibodies against the virus, cellular immunity also plays a crucial role in the fight against IAVs. On the other hand, IAVs have developed multiple strategies to escape from host immune surveillance for successful replication. In this review, we discuss how immune system, especially innate immune system and critical molecules are involved in the antiviral defense against IAVs. In addition, we highlight how IAVs antagonize different immune responses to achieve a successful infection.

Keywords: adaptive immunity; immune evasion; immune response; influenza A virus; innate immunity.

Figure 1

Schematic diagram for innate immune response against influenza A virus (IAV) infection. Intracellular detection of IAV infection by the host pathogen recognition receptors (PRRs) activates transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells, interferon regulatory factor 3 (IRF3), and IRF7. The PRRs include retinoic acid-inducible gene-I protein, melanoma differentiation-associated gene 5, and toll-like receptors. Then these activated transcription factors trigger the expression of type I and type III interferons (IFNs). IFNs secreted by the infected cells interact with their receptors, which results in activation of Janus kinase-signal transducer and activator of transcription signaling pathway that governs the expression of various IFN-stimulated genes.