Yi-Tsen Lin1,2, Chih-Feng Lin1, Te-Huei Yeh1,3. 1. Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan. 2. Graduate School of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. 3. Department of Otolaryngology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Abstract
Background: Nasal epithelial cells are the first site of encounter of the influenza virus, and their innate immune response might define subsequent inflammatory direction.Aims/objectives: We used metabolomics analysis to identify metabolic changes and the regulation of inflammatory cytokines in nasal epithelial cells upon influenza virus infection.Material and methods: We cultured nasal epithelial cells using air-liquid interface (ALI) model. Influenza virus (PR8) infection followed by metabolomic analysis was performed. Furthermore, cytokine expression was analyzed by cytokine array and RT-qPCR. Results: Metabolomic analysis revealed depletion of the tryptophan and accumulation of its metabolite, kynurenine, within 48 h. The major enzyme involved in the tryptophan metabolic pathway, indoleamine 2,3-dioxygenase (IDO), was overexpressed after infection. Cytokine expression array after infection showed increased levels of IL-1α, CCL2, IL-6, CXCL10, CCL5, and CXCL11, and after using 1-methyltryptophan (1-MT) as inhibitor, the expression levels of IL-6 and G-CSF were reduced.Conclusions and significance: Viral infection results in depletion of tryptophan and accumulation of kynurenine via increased cellular IDO activity. Inhibition of IDO activity or replenishment of tryptophan by local application may be a good therapeutic strategy for limiting the initial damage caused by influenza virus in nasal epithelial cells.
Background: Nasal epithelial cells are the first site of encounter of the influenza virus, and their innate immune response might define subsequent inflammatory direction.Aims/objectives: We used metabolomics analysis to identify metabolic changes and the regulation of inflammatory cytokines in nasal epithelial cells upon influenza virus infection.Material and methods: We cultured nasal epithelial cells using air-liquid interface (ALI) model. Influenza virus (PR8) infection followed by metabolomic analysis was performed. Furthermore, cytokine expression was analyzed by cytokine array and RT-qPCR. Results: Metabolomic analysis revealed depletion of the tryptophan and accumulation of its metabolite, kynurenine, within 48 h. The major enzyme involved in the tryptophan metabolic pathway, indoleamine 2,3-dioxygenase (IDO), was overexpressed after infection. Cytokine expression array after infection showed increased levels of IL-1α, CCL2, IL-6, CXCL10, CCL5, and CXCL11, and after using 1-methyltryptophan (1-MT) as inhibitor, the expression levels of IL-6 and G-CSF were reduced.Conclusions and significance: Viral infection results in depletion of tryptophan and accumulation of kynurenine via increased cellular IDO activity. Inhibition of IDO activity or replenishment of tryptophan by local application may be a good therapeutic strategy for limiting the initial damage caused by influenza virus in nasal epithelial cells.
Authors: Fernanda Martins Marim; Danielle Cunha Teixeira; Celso Martins Queiroz-Junior; Bruno Vinicius Santos Valiate; Jose Carlos Alves-Filho; Thiago Mattar Cunha; Robert Dantzer; Mauro Martins Teixeira; Antonio Lucio Teixeira; Vivian Vasconcelos Costa Journal: Front Immunol Date: 2021-07-15 Impact factor: 7.561