Back to Search
Start Over
Influenza-induced Tpl2 expression within alveolar epithelial cells is dispensable for host viral control and anti-viral immunity
- Source :
- PLoS ONE, Vol 17, Iss 1, p e0262832 (2022), PLoS ONE
- Publication Year :
- 2022
- Publisher :
- Public Library of Science (PLoS), 2022.
-
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.
- Subjects :
- RNA viruses
Male
Viral Diseases
Physiology
Biochemistry
Epithelium
Madin Darby Canine Kidney Cells
Mice
Medical Conditions
Animal Cells
Immune Physiology
Medicine and Health Sciences
Immune Response
Pathology and laboratory medicine
Mice, Knockout
Innate Immune System
Multidisciplinary
Animal Models
Medical microbiology
respiratory system
MAP Kinase Kinase Kinases
Infectious Diseases
Experimental Organism Systems
Influenza A virus
Viruses
Cytokines
Medicine
Female
Cellular Types
Anatomy
Pathogens
Research Article
Science
Immunology
Mouse Models
Research and Analysis Methods
Microbiology
Model Organisms
Signs and Symptoms
Dogs
Orthomyxoviridae Infections
Proto-Oncogene Proteins
Influenza viruses
Animals
Inflammation
Host Microbial Interactions
Organisms
Viral pathogens
Biology and Life Sciences
Proteins
Epithelial Cells
Cell Biology
Molecular Development
Influenza
Microbial pathogens
Health Care
Mice, Inbred C57BL
Disease Models, Animal
Biological Tissue
Immune System
Alveolar Epithelial Cells
Animal Studies
Interferons
Health Statistics
Morbidity
Clinical Medicine
Orthomyxoviruses
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 17
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....33793504ec379f73bfc436bfda9dbaab