MilliporeSigma
  • Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium.

Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium.

iScience (2021-11-09)
Jacob Thyrsted, Jacob Storgaard, Julia Blay-Cadanet, Alexander Heinz, Anne Laugaard Thielke, Stefania Crotta, Frank de Paoli, David Olagnier, Andreas Wack, Karsten Hiller, Anne Louise Hansen, Christian Kanstrup Holm
ABSTRACT

Pathogenic viruses induce metabolic changes in host cells to secure the availability of biomolecules and energy to propagate. Influenza A virus (IAV) and severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) both infect the human airway epithelium and are important human pathogens. The metabolic changes induced by these viruses in a physiologically relevant human model and how this affects innate immune responses to limit viral propagation are not well known. Using an ex vivo model of pseudostratified primary human airway epithelium, we here demonstrate that infection with both IAV and SARS-CoV-2 resulted in distinct metabolic changes including increases in lactate dehydrogenase A (LDHA) expression and LDHA-mediated lactate formation. Interestingly, LDHA regulated both basal and induced mitochondrial anti-viral signaling protein (MAVS)-dependent type I interferon (IFN) responses to promote IAV, but not SARS-CoV-2, replication. Our data demonstrate that LDHA and lactate promote IAV but not SARS-CoV-2 replication by inhibiting MAVS-dependent induction of type I IFN in primary human airway epithelium.

MATERIALS
Product Number
Brand
Product Description

SAFC
Formaldehyde solution, contains 10-15% methanol as stabilizer, 37 wt. % in H2O
Sigma-Aldrich
Fluorescein isothiocyanate–dextran, average mol wt 4,000, (FITC:Glucose = 1:250)
Sigma-Aldrich
RPMI-1640 Medium, With L-glutamine and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Dulbecco′s Modified Eagle′s Medium - high glucose, With 4500 mg/L glucose, L-glutamine, sodium pyruvate, and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Dulbecco′s Modified Eagle′s Medium - low glucose, With 1000 mg/L glucose, and sodium bicarbonate, without L-glutamine and phenol red, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
TWEEN® 20, viscous liquid
Millipore
Benzonase® Nuclease, ≥250 units/μL, ≥90% (SDS-PAGE), recombinant, expressed in E. coli, buffered aqueous glycerol solution