4 results on '"Scott E. Evans"'
Search Results
2. Inducible Lung Epithelial Resistance Requires Multisource Reactive Oxygen Species Generation To Protect against Viral Infections
- Author
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Carson T. Kirkpatrick, Yongxing Wang, Miguel M. Leiva Juarez, Pooja Shivshankar, Jezreel Pantaleón García, Alexandria K. Plumer, Vikram V. Kulkarni, Hayden H. Ware, Fahad Gulraiz, Miguel A. Chavez Cavasos, Gabriela Martinez Zayas, Shradha Wali, Andrew P. Rice, Hongbing Liu, James M. Tour, William K. A. Sikkema, Ana S. Cruz Solbes, Keith A. Youker, Michael J. Tuvim, Burton F. Dickey, and Scott E. Evans
- Subjects
inducible resistance ,Toll-like receptors ,lung epithelium ,mucosal immunity ,reactive oxygen species ,viral pneumonia ,Microbiology ,QR1-502 - Abstract
ABSTRACT Viral pneumonias cause profound worldwide morbidity, necessitating novel strategies to prevent and treat these potentially lethal infections. Stimulation of intrinsic lung defenses via inhalation of synergistically acting Toll-like receptor (TLR) agonists protects mice broadly against pneumonia, including otherwise-lethal viral infections, providing a potential opportunity to mitigate infectious threats. As intact lung epithelial TLR signaling is required for the inducible resistance and as these cells are the principal targets of many respiratory viruses, the capacity of lung epithelial cells to be therapeutically manipulated to function as autonomous antiviral effectors was investigated. Our work revealed that mouse and human lung epithelial cells could be stimulated to generate robust antiviral responses that both reduce viral burden and enhance survival of isolated cells and intact animals. The antiviral protection required concurrent induction of epithelial reactive oxygen species (ROS) from both mitochondrial and dual oxidase sources, although neither type I interferon enrichment nor type I interferon signaling was required for the inducible protection. Taken together, these findings establish the sufficiency of lung epithelial cells to generate therapeutically inducible antiviral responses, reveal novel antiviral roles for ROS, provide mechanistic insights into inducible resistance, and may provide an opportunity to protect patients from viral pneumonia during periods of peak vulnerability. IMPORTANCE Viruses are the most commonly identified causes of pneumonia and inflict unacceptable morbidity, despite currently available therapies. While lung epithelial cells are principal targets of respiratory viruses, they have also been recently shown to contribute importantly to therapeutically inducible antimicrobial responses. This work finds that lung cells can be stimulated to protect themselves against viral challenges, even in the absence of leukocytes, both reducing viral burden and improving survival. Further, it was found that the protection occurs via unexpected induction of reactive oxygen species (ROS) from spatially segregated sources without reliance on type I interferon signaling. Coordinated multisource ROS generation has not previously been described against viruses, nor has ROS generation been reported for epithelial cells against any pathogen. Thus, these findings extend the potential clinical applications for the strategy of inducible resistance to protect vulnerable people against viral infections and also provide new insights into the capacity of lung cells to protect against infections via novel ROS-dependent mechanisms.
- Published
- 2018
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3. Erratum for Kirkpatrick et al., 'Inducible Lung Epithelial Resistance Requires Multisource Reactive Oxygen Species Generation To Protect against Viral Infections'
- Author
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Keith A. Youker, Pooja Shivshankar, William K.A. Sikkema, Andrew P. Rice, Hayden H. Ware, Alexandria K. Plumer, Yongxing Wang, Gabriela Martinez Zayas, James M. Tour, Shradha Wali, Miguel A. Chavez Cavasos, Vikram V. Kulkarni, Carson T. Kirkpatrick, Burton F Dickey, Jezreel Pantaleón García, Fahad Gulraiz, Miguel M. Leiva Juarez, Michael J. Tuvim, Hongbing Liu, Scott E. Evans, and Ana S. Cruz Solbes
- Subjects
Male ,viral pneumonia ,Biology ,Microbiology ,lung epithelium ,Mice ,03 medical and health sciences ,Virology ,Influenza, Human ,medicine ,Animals ,Humans ,Lung ,030304 developmental biology ,0303 health sciences ,030306 microbiology ,Influenza A Virus, H3N2 Subtype ,Toll-Like Receptors ,inducible resistance ,Epithelial Cells ,Molecular biology ,QR1-502 ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Interferon Type I ,Reactive oxygen species generation ,mucosal immunity ,Female ,Erratum ,Reactive Oxygen Species ,Research Article - Abstract
Viral pneumonias cause profound worldwide morbidity, necessitating novel strategies to prevent and treat these potentially lethal infections. Stimulation of intrinsic lung defenses via inhalation of synergistically acting Toll-like receptor (TLR) agonists protects mice broadly against pneumonia, including otherwise-lethal viral infections, providing a potential opportunity to mitigate infectious threats. As intact lung epithelial TLR signaling is required for the inducible resistance and as these cells are the principal targets of many respiratory viruses, the capacity of lung epithelial cells to be therapeutically manipulated to function as autonomous antiviral effectors was investigated. Our work revealed that mouse and human lung epithelial cells could be stimulated to generate robust antiviral responses that both reduce viral burden and enhance survival of isolated cells and intact animals. The antiviral protection required concurrent induction of epithelial reactive oxygen species (ROS) from both mitochondrial and dual oxidase sources, although neither type I interferon enrichment nor type I interferon signaling was required for the inducible protection. Taken together, these findings establish the sufficiency of lung epithelial cells to generate therapeutically inducible antiviral responses, reveal novel antiviral roles for ROS, provide mechanistic insights into inducible resistance, and may provide an opportunity to protect patients from viral pneumonia during periods of peak vulnerability., IMPORTANCE Viruses are the most commonly identified causes of pneumonia and inflict unacceptable morbidity, despite currently available therapies. While lung epithelial cells are principal targets of respiratory viruses, they have also been recently shown to contribute importantly to therapeutically inducible antimicrobial responses. This work finds that lung cells can be stimulated to protect themselves against viral challenges, even in the absence of leukocytes, both reducing viral burden and improving survival. Further, it was found that the protection occurs via unexpected induction of reactive oxygen species (ROS) from spatially segregated sources without reliance on type I interferon signaling. Coordinated multisource ROS generation has not previously been described against viruses, nor has ROS generation been reported for epithelial cells against any pathogen. Thus, these findings extend the potential clinical applications for the strategy of inducible resistance to protect vulnerable people against viral infections and also provide new insights into the capacity of lung cells to protect against infections via novel ROS-dependent mechanisms.
- Published
- 2019
4. Inducible Lung Epithelial Resistance Requires Multisource Reactive Oxygen Species Generation To Protect against Viral Infections
- Author
-
Miguel A. Chavez Cavasos, Carson T. Kirkpatrick, Ana S. Cruz Solbes, Fahad Gulraiz, James M. Tour, Jezreel Pantaleón García, Gabriela Martinez Zayes, William K.A. Sikkema, Miguel M. Leiva Juarez, Hayden H. Ware, Michael J. Tuvim, Vikram V. Kulkarni, Andrew P. Rice, Hongbing Liu, Scott E. Evans, Burton F Dickey, Pooja Shivshankar, Yongxing Wang, Keith A. Youker, Shradha Wali, and Alexandria K. Plumer
- Subjects
0301 basic medicine ,viral pneumonia ,Biology ,Microbiology ,lung epithelium ,03 medical and health sciences ,Interferon ,Virology ,medicine ,Pathogen ,reactive oxygen species ,chemistry.chemical_classification ,Reactive oxygen species ,Lung ,Effector ,inducible resistance ,medicine.disease ,QR1-502 ,Toll-like receptors ,3. Good health ,Pneumonia ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Viral pneumonia ,Immunology ,mucosal immunity ,Viral load ,medicine.drug - Abstract
Viral pneumonias cause profound worldwide morbidity, necessitating novel strategies to prevent and treat these potentially lethal infections. Stimulation of intrinsic lung defenses via inhalation of synergistically acting Toll-like receptor (TLR) agonists protects mice broadly against pneumonia, including otherwise-lethal viral infections, providing a potential opportunity to mitigate infectious threats. As intact lung epithelial TLR signaling is required for the inducible resistance and as these cells are the principal targets of many respiratory viruses, the capacity of lung epithelial cells to be therapeutically manipulated to function as autonomous antiviral effectors was investigated. Our work revealed that mouse and human lung epithelial cells could be stimulated to generate robust antiviral responses that both reduce viral burden and enhance survival of isolated cells and intact animals. The antiviral protection required concurrent induction of epithelial reactive oxygen species (ROS) from both mitochondrial and dual oxidase sources, although neither type I interferon enrichment nor type I interferon signaling was required for the inducible protection. Taken together, these findings establish the sufficiency of lung epithelial cells to generate therapeutically inducible antiviral responses, reveal novel antiviral roles for ROS, provide mechanistic insights into inducible resistance, and may provide an opportunity to protect patients from viral pneumonia during periods of peak vulnerability. IMPORTANCE Viruses are the most commonly identified causes of pneumonia and inflict unacceptable morbidity, despite currently available therapies. While lung epithelial cells are principal targets of respiratory viruses, they have also been recently shown to contribute importantly to therapeutically inducible antimicrobial responses. This work finds that lung cells can be stimulated to protect themselves against viral challenges, even in the absence of leukocytes, both reducing viral burden and improving survival. Further, it was found that the protection occurs via unexpected induction of reactive oxygen species (ROS) from spatially segregated sources without reliance on type I interferon signaling. Coordinated multisource ROS generation has not previously been described against viruses, nor has ROS generation been reported for epithelial cells against any pathogen. Thus, these findings extend the potential clinical applications for the strategy of inducible resistance to protect vulnerable people against viral infections and also provide new insights into the capacity of lung cells to protect against infections via novel ROS-dependent mechanisms.
- Published
- 2018
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