RSV immunizes bystander cells to IAV infection using interferons β and λ

2021 ◽  
Author(s):  
Maciej Czerkies ◽  
Marek Kochańczyk ◽  
Zbigniew Korwek ◽  
Wiktor Prus ◽  
Tomasz Lipniacki
Keyword(s):  
Cell Population ◽  
Influenza A ◽  
Population Level ◽  
Alveolar Epithelial Cells ◽  
Subsequent Infection ◽  
Alveolar Epithelial ◽  
Host Innate Immune Response ◽  
Maximum Protection ◽  
Syncytial Virus ◽  
Protection Against Infection

We observed the interference between two prevalent respiratory viruses, respiratory syncytial virus (RSV) and influenza A virus (IAV, H1N1), and characterized its molecular underpinnings in alveolar epithelial cells (A549). We found that RSV induces higher interferon (IFN) β production than IAV and that IFNβ priming confers higher protection against infection with IAV than with RSV. Consequently, we focused on the sequential infection scheme: RSV-then-IAV. Using the A549 WT, IFNAR1 KO, IFNLR1 KO, and IFNAR1–IFNLR1 double KO cell lines we found that both IFNβ and IFNλ are necessary for maximum protection against subsequent infection. Immunostaining revealed that preinfection with RSV partitions the cell population into a subpopulation susceptible to subsequent infection with IAV and an IAV-proof subpopulation. Strikingly, the susceptible cells turned out to be those already compromised and efficiently expressing RSV, whereas the bystander, interferon-primed cells are resistant to IAV infection. Thus, the virus–virus exclusion at the cell population level is not realized through a direct competition for a shared ecological niche (single cell) but rather achieved with the involvement of specific cytokines induced within the host innate immune response.

scholarly journals Influenza A Virus-Infected Hosts Boost an Invasive Type of Streptococcus pyogenes Infection in Mice

2003 ◽  
Vol 77 (7) ◽  
pp. 4104-4112 ◽  
Author(s):  
Shigefumi Okamoto ◽  
Shigetada Kawabata ◽  
Ichiro Nakagawa ◽  
Yoshinobu Okuno ◽  
Toshiyuki Goto ◽  
...  
Keyword(s):  
Necrotizing Fasciitis ◽  
Influenza A Virus ◽  
Streptococcus Pyogenes ◽  
Death Rate ◽  
Influenza A ◽  
Alveolar Epithelial Cells ◽  
Toxic Shock ◽  
Alveolar Epithelial ◽  
Viral Hemagglutinin ◽  
Prior Infection

ABSTRACT The apparent worldwide resurgence of invasive Streptococcus pyogenes infection in the last two decades remains unexplained. At present, animal models in which toxic shock-like syndrome or necrotizing fasciitis is induced after S. pyogenes infection are not well developed. We demonstrate here that infection with a nonlethal dose of influenza A virus 2 days before intranasal infection with a nonlethal dose of S. pyogenes strains led to a death rate of more than 90% in mice, 10% of which showed necrotizing fasciitis. Infection of lung alveolar epithelial cells by the influenza A virus resulted in viral hemagglutinin expression on the cell surface and promoted internalization of S. pyogenes. However, treatment with monoclonal antibodies to hemagglutinin markedly decreased this internalization. Our results indicate that prior infection with influenza A virus induces a lethal synergism, resulting in the induction of invasive S. pyogenes infection in mice.

scholarly journals Influenza virus infection alters ion channel function of airway and alveolar cells: mechanisms and physiological sequelae

2017 ◽  
Vol 313 (5) ◽  
pp. L845-L858 ◽  
Author(s):  
James David Londino ◽  
Ahmed Lazrak ◽  
James F. Collawn ◽  
Zsuzsanna Bebok ◽  
Kevin S. Harrod ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Bacterial Infections ◽  
Alveolar Epithelial Cell ◽  
Ionic Composition ◽  
Influenza Virus Infection ◽  
Alveolar Epithelial Cells ◽  
Alveolar Cells ◽  
Alveolar Epithelial

The cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial sodium channels (ENaC) are located in the apical membranes of airway and alveolar epithelial cells. These transporters play an important role in the regulation of lung fluid balance across airway and alveolar epithelia by being the conduits for chloride (Cl−) and bicarbonate ([Formula: see text]) secretion and sodium (Na+) ion absorption, respectively. The functional role of these channels in the respiratory tract is to maintain the optimum volume and ionic composition of the bronchial periciliary fluid (PCL) and alveolar lining fluid (ALF) layers. The PCL is required for proper mucociliary clearance of pathogens and debris, and the ALF is necessary for surfactant homeostasis and optimum gas exchange. Dysregulation of ion transport may lead to mucus accumulation, bacterial infections, inflammation, pulmonary edema, and compromised respiratory function. Influenza (or flu) in mammals is caused by influenza A and B viruses. Symptoms include dry cough, sore throat, and is often followed by secondary bacterial infections, accumulation of fluid in the alveolar spaces and acute lung injury. The underlying mechanisms of flu symptoms are not fully understood. This review summarizes our present knowledge of how influenza virus infections alter airway and alveolar epithelial cell CFTR and ENaC function in vivo and in vitro and the role of these changes in influenza pathogenesis.

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