Innate Immune Responses to Influenza Virus Infections in the Upper Respiratory Tract

Abstract

The innate immune system is the host's first line of immune defence against any invading pathogen. To establish an infection in a human host the influenza virus must replicate in epithelial cells of the upper respiratory tract. However, there are several innate immune mechanisms in place to stop the virus from reaching epithelial cells. In addition to limiting viral replication and dissemination, the innate immune system also activates the adaptive immune system leading to viral clearance, enabling the respiratory system to return to normal homeostasis. However, an overzealous innate immune system or adaptive immune response can be associated with immunopathology and aid secondary bacterial infections of the lower respiratory tract leading to pneumonia. In this review, we discuss the mechanisms utilised by the innate immune system to limit influenza virus replication and the damage caused by influenza viruses on the respiratory tissues and how these very same protective immune responses can cause immunopathology.

Keywords: influenza virus; innate immune system; upper respiratory tract.

Figure 1

Schematic of human upper respiratory tract. In humans, the upper respiratory tract (URT) consists of the nose, sinuses, pharynx, and larynx. The lower respiratory tract (LRT) includes as the trachea and lungs. Influenza virus infection primarily occurs in the URT, where the virus must first overcome the mucus layer to infect underlying epithelial cells. Influenza virus infections generally cause a self-limiting infection in the URT, but the virus does have the ability to replicate in the trachea and the lungs. Image made using BioRender.

Figure 2

Localisation of PRRs responsible for influenza viral recognition. Schematic of PRRs responsible for viral recognition. The inflammasome requires two signals for activation and are shaded green and yellow, respectively. Image made using BioRender.