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Review
. 2021 Jul;110(1):115-122.
doi: 10.1002/JLB.4RU0820-232R. Epub 2020 Sep 8.

From virus to inflammation, how influenza promotes lung damage

Mitchell Klomp  1 , Sumit Ghosh  2 , Sohail Mohammed  3 , M Nadeem Khan  1
Affiliations
Review

From virus to inflammation, how influenza promotes lung damage

Mitchell Klomp et al. J Leukoc Biol. 2021 Jul.

Abstract

Despite seasonal vaccines, influenza-related hospitalization and death rates have remained unchanged over the past 5 years. Influenza pathogenesis has 2 crucial clinical components; first, influenza causes acute lung injury that may require hospitalization. Second, acute injury promotes secondary bacterial pneumonia, a leading cause of hospitalization and disease burden in the United States and globally. Therefore, developing an effective therapeutic regimen against influenza requires a comprehensive understanding of the damage-associated immune-mechanisms to identify therapeutic targets for interventions to mitigate inflammation/tissue-damage, improve antiviral immunity, and prevent influenza-associated secondary bacterial diseases. In this review, the pathogenic immune mechanisms implicated in acute lung injury and the possibility of using lung inflammation and barrier crosstalk for developing therapeutics against influenza are highlighted.

Keywords: inflammation; influenza; lung pathology.

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Conflict of interest statement

Conflict of Interest. The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Incidence of Influenza virus infections for the years 2014 to 2019. Data courtesy of the CDC.
Figure 2.
Figure 2.
Tumor-necrosis-factor receptor apoptosis-inducing ligand (TRAIL) and Fas Ligand interactions with their respective receptors on epithelial cells in the lungs, along with type I and Type III interferons (IFN), result in the induction of either apoptosis or necroptosis as a means of epithelial cell death. Influenza A virus (IAV) predisposes the epithelial cells in the lungs towards cell death suggesting the epithelial cell-monocyte interactions further drive lung damage.
Figure 3.
Figure 3.
Inflammation induced by epithelial cell recognition of influenza virus or interactions with proinflammatory immune cells in the lungs results in weakening tight junction barriers and thereby increasing vascular permeability. These cell-cell interactions also result in epithelial cell death which further weakens the epithelial cell barriers and leads to a more permissive state for bacterial infections.
See this image and copyright information in PMC

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