Infect Chemother.  2013 Mar;45(1):11-21.

The Battle Between Influenza and the Innate Immune Response in the Human Respiratory Tract

• Nicholls J

Abstract

Influenza is a viral infection of the respiratory tract. Infection is normally confined to the upper respiratory tract but certain viral strains have evolved the ability to infect the lower respiratory tract, including the alveoli, leading to inflammation and a disease pattern of diffuse alveolar damage. Factors leading to this sequence of events are novel influenza strains, or strains that have viral proteins, in particular the NS1 protein that allow it to escape the innate immune system. There are three main barriers that prevent infection of pneumocytes - mucin, host defence lectins and cells such as macrophages. Viruses have developed strategies such as neuraminidase and glycosylation patterns that allow this evasion. Though there has been much investment in antiviral drugs, it is proposed that more attention should be directed towards developing or utilizing compounds that enhance the ability of the innate immune system to combat viral infection.

Keyword

Influenza; Innate Immunity; Mucin; Lectin; RIG-I

MeSH Terms

Antiviral Agents
Glycosylation
Humans
Immune System
Immunity, Innate
Inflammation
Influenza, Human
Investments
Lectins
Macrophages
Mucins
Neuraminidase
Pneumocytes
Respiratory System
United Nations
Viral Proteins
Antiviral Agents
Lectins
Mucins
Neuraminidase
Viral Proteins

Figure

• 

  Figure 1 The first barrier to infection - mucin. Mucicarmine stained section of the normal human bronchus showing goblet cells and submucous glands containing purple staining mucin. Avian influenza viruses preferentially bind to goblet cells while human viruses bind to ciliated cells. Inset shows the interaction of viral haamagglutinin with the sialic acid terminated glycoprotein present on the surface of cells.

• 

  Figure 2 The second barrier to infection - host defence lectins. Section of the normal human bronchiole and alveoli with red colour indicating the presence of 2-6 terminated sialic acid. Insets show surfactant protein A and D (SP-A and SP-D) bind to influenza viruses in two ways. The SP-A is sialylated and so acts as a decoy receptor. SP-D recognizes the galactose or mannose present on the surface of the influenza viruses. Macrophages also recognize the mannose present on viruses.

• 

  Figure 3 Intracellular activation of the RIG-I pathway. Electron micrograph of human ex vivo tissues infected with avian influenza virus showing egress of viral particles from type 2 pneumocytes. The viral RNA binds to RIG-I and is then ubiquitinated by TRIM25 allowing binding to MAVS followed by activation of TBK-1, IKK pathways and transcription of interferon. The release of interferon leads to increased cytokine production, recruitment of neutrophils and activation of macrophages. The interferon will act as an autocrine and paracrine function leading to more cytokine and antiviral proteins.

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