Abstract
There is abundant evidence that the innate immune response to influenza A virus (IAV) is highly complex and plays a key role in protection against IAV induced infection and illness. Unfortunately it also clear that aspects of innate immunity can lead to severe morbidity or mortality from IAV, including inflammatory lung injury, bacterial superinfection, and exacerbation of reactive airways disease. We review broadly the virus and host factors that result in adverse outcomes from IAV and show evidence that inflammatory responses can become damaging even apart from changes in viral replication per se, with special focus on the positive and adverse effects of neutrophils and monocytes. We then evaluate in detail the role of soluble innate inhibitors including surfactant protein D and antimicrobial peptides that have a potential dual capacity for down-regulating viral replication and also inhibiting excessive inflammatory responses and how these innate host factors could possibly be harnessed to treat IAV infection. Where appropriate we draw comparisons and contrasts the SARS-CoV viruses and IAV in an effort to point out where the extensive knowledge existing regarding severe IAV infection could help guide research into severe COVID 19 illness or vice versa.
Highlights
There is a vast, and still growing, literature on the pathogenesis of severe influenza A virus (IAV) infection
Our major focus for this review will be on severe IAV such as is seen during pandemic infection or avian influenza infection, and we will focus primarily on specific aspects of the immune response that we have studied that may relate to future treatments
We have studied a variety of innate soluble inhibitors of IAV most notably, the collectins and antimicrobial peptides
Summary
There is a vast, and still growing, literature on the pathogenesis of severe IAV infection. Seasonal IAV tends to be somewhat attenuated due to adaptations made for sustained maintenance in humans and due to partial immunity against them, highly pathogenic coronavirus infections resemble more closely novel pandemic IAV strains in that humans are immunologically largely naïve to them. These factors leave innate immunity with a key role in bridging the gap between initial infection and onset of cell and antibody mediated immunity for both IAV and novel coronaviruses. Where appropriate draw comparisons or contrasts to COVID-19, since knowledge of severe IAV pathogenesis may allow a more rapid discovery of aspects of pathogenesis of severe COVID 19 and treatments being tested for COVID-19 may prove beneficial for severe IAV as well (see Table 1)
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