Distinct roles for MDA5 and TLR3 in the acute response to inhaled double-stranded RNA
| Autor: | Steve N. Georas, Janelle Veazey, Sophia Eliseeva, Timothy Smyth, Timothy J. Chapman, Sara E. Hillman |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Interferon-Induced Helicase IFIH1 Pulmonology Neutrophils Physiology Pathology and Laboratory Medicine Biochemistry Mice White Blood Cells Mathematical and Statistical Techniques 0302 clinical medicine Animal Cells Medicine and Health Sciences Immune Response Barrier function Chemokine CCL3 Mice Knockout Toll-like receptor Multidisciplinary Respiration Statistics MDA5 3. Good health Cell biology Nucleic acids medicine.anatomical_structure Inhalation Physical Sciences Medicine Female Cellular Types medicine.symptom Bronchoalveolar Lavage Fluid Research Article Science Immune Cells Immunology Inflammation Respiratory Mucosa Double stranded RNA Research and Analysis Methods Microbiology Interferon-gamma 03 medical and health sciences Signs and Symptoms Immune system Diagnostic Medicine Albumins Virology Administration Inhalation medicine Animals Statistical Methods RNA Double-Stranded Analysis of Variance Blood Cells Lung Interleukin-6 business.industry Biology and Life Sciences Proteins Cell Biology Toll-Like Receptor 3 Mice Inbred C57BL 030104 developmental biology Respiratory Infections TLR3 RNA Physiological Processes business Airway Mathematics Viral Transmission and Infection 030215 immunology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 14, Iss 5, p e0216056 (2019) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0216056 |
| Popis: | The airway epithelial barrier is critical for preventing pathogen invasion and translocation of inhaled particles into the lung. Epithelial cells also serve an important sentinel role after infection and release various pro-inflammatory mediators that recruit and activate immune cells. Airway epithelial barrier disruption has been implicated in a growing number of respiratory diseases including viral infections. It is thought that when a pathogen breaks the barrier and gains access to the host tissue, pro-inflammatory mediators increase, which further disrupts the barrier and initiates a vicious cycle of leak. However, it is difficult to study airway barrier integrity in vivo, and little is known about relationship between epithelial barrier function and airway inflammation. Current assays of pulmonary barrier integrity quantify the leak of macromolecules from the vasculature into the airspaces (or "inside/out" leak). However, it is also important to measure the ease with which inhaled particles, allergens, or pathogens can enter the subepithelial tissues (or "outside/in" leak). We challenged mice with inhaled double stranded RNA (dsRNA) and explored the relationship between inside/out and outside/in barrier function and airway inflammation. Using wild-type and gene-targeted mice, we studied the roles of the dsRNA sensors Toll Like Receptor 3 (TLR3) and Melanoma Differentiation-Associated protein 5 (MDA5). Here we report that after acute challenge with inhaled dsRNA, airway barrier dysfunction occurs in a TLR3-dependent manner, whereas leukocyte accumulation is largely MDA5-dependent. We conclude that airway barrier dysfunction and inflammation are regulated by different mechanisms at early time points after exposure to inhaled dsRNA. |
| Databáze: | OpenAIRE |
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