PT  - JOURNAL ARTICLE
AU  - T Berger
AU  - C F Garcia Castro
AU  - V Lakshmi
AU  - S Völkel
AU  - N Sommer
AU  - C Skevaki
TI  - Enhanced early T cell activation and protection from hyper-inflammation in smoke exposed Cox4i2−/− infected mice with influenza
AID  - 10.1183/13993003.congress-2022.4483
DP  - 2022 Sep 04
TA  - European Respiratory Journal
PG  - 4483
VI  - 60
IP  - suppl 66
4099  - http://erj.ersjournals.com/content/60/suppl_66/4483.short
4100  - http://erj.ersjournals.com/content/60/suppl_66/4483.full
SO  - Eur Respir J2022 Sep 04; 60
AB  - Respiratory virus infections are a major cause of concern in chronic obstructive pulmonary disease (COPD). Mitochondrial reactive oxygen species (mtROS) play an important role in immune function and increased mtROS levels may have an effect in COPD. Cox4i2 regulates ROS production at complex III and has been shown implicated in the development of emphysema.We hypothesize that Cox4i2−/− mice are protected from smoke-induced hyper-inflammation but also exhibit impaired T cell activation and antiviral immunity.We analyzed T cell subsets, BAL Albumin leakage and virus load via qPCR. C57BL/6 (WT) and Cox4i2−/− mice were exposed for two weeks to smoke (CS) or room air (RA), with or without H1N1 influenza A/Puerto Rico/8/1934 (PR8) infection. Mice were sacrificed 3 and 10 days post infection (DPI).There was no difference in viral load at 3 DPI, but at 10 DPI WT CS mice showed higher virus load when compared to WT RA mice. Infection led to increased albumin leakage in all groups but not Cox4i2−/− CS mice. CD69 on CD4+ T cells increased after infection, particularly in CS Cox4i2−/− mice vs. both WT groups at 3 DPI. In CD8+ T cells Cox4i2−/− CS mice showed similar CD69 upregulation as WT RA mice. Intracellular staining of IFN-γ in CD8+ T Cells was lower in both Cox4i2−/− groups at 10 DPI. Restimulation with virus peptide showed impaired IFN-γ production in both Cox4i2−/− groups and WT CS mice at 10 DPI.Taken together Cox4i2−/− did not show impaired T cell activation albeit decreased albumin leakage and IFN-γ production at 10 DPI indicate a protection effect over hyper-inflammation, especially in Cox4i2−/− CS mice.FootnotesCite this article as Eur Respir J 2022; 60: Suppl. 66, 4483.This article was presented at the 2022 ERS International Congress, in session “-”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).