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Influenza-induced Tpl2 expression within alveolar epithelial cells is dispensable for host viral control and anti-viral immunity.
Wyatt, Kara D; Sarr, Demba; Sakamoto, Kaori; Watford, Wendy T.
  • Wyatt KD; Department of Infectious Diseases, University of Georgia, Athens, Georgia, United States of America.
  • Sarr D; Department of Infectious Diseases, University of Georgia, Athens, Georgia, United States of America.
  • Sakamoto K; Department of Pathology, University of Georgia, Athens, Georgia, United States of America.
  • Watford WT; Department of Infectious Diseases, University of Georgia, Athens, Georgia, United States of America.
PLoS One ; 17(1): e0262832, 2022.
Article in English | MEDLINE | ID: covidwho-1643286
ABSTRACT
Tumor progression locus 2 (Tpl2) is a serine/threonine kinase that regulates the expression of inflammatory mediators in response to Toll-like receptors (TLR) and cytokine receptors. Global ablation of Tpl2 leads to severe disease in response to influenza A virus (IAV) infection, characterized by respiratory distress, and studies in bone marrow chimeric mice implicated Tpl2 in non-hematopoietic cells. Lung epithelial cells are primary targets and replicative niches of influenza viruses; however, the specific regulation of antiviral responses by Tpl2 within lung epithelial cells has not been investigated. Herein, we show that Tpl2 is basally expressed in primary airway epithelial cells and that its expression increases in both type I and type II airway epithelial cells (AECI and AECII) in response to influenza infection. We used Nkx2.1-cre to drive Tpl2 deletion within pulmonary epithelial cells to delineate epithelial cell-specific functions of Tpl2 during influenza infection in mice. Although modest increases in morbidity and mortality were attributed to cre-dependent deletion in lung epithelial cells, no alterations in host cytokine production or lung pathology were observed. In vitro, Tpl2 inhibition within the type I airway epithelial cell line, LET1, as well as genetic ablation in primary airway epithelial cells did not alter cytokine production. Overall, these findings establish that Tpl2-dependent defects in cells other than AECs are primarily responsible for the morbidity and mortality seen in influenza-infected mice with global Tpl2 ablation.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Influenza A virus / Proto-Oncogene Proteins / Orthomyxoviridae Infections / MAP Kinase Kinase Kinases / Alveolar Epithelial Cells / Host Microbial Interactions Type of study: Prognostic study Limits: Animals Language: English Journal: PLoS One Journal subject: Science / Medicine Year: 2022 Document Type: Article Affiliation country: Journal.pone.0262832

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Influenza A virus / Proto-Oncogene Proteins / Orthomyxoviridae Infections / MAP Kinase Kinase Kinases / Alveolar Epithelial Cells / Host Microbial Interactions Type of study: Prognostic study Limits: Animals Language: English Journal: PLoS One Journal subject: Science / Medicine Year: 2022 Document Type: Article Affiliation country: Journal.pone.0262832