Dendritic cell molecules within the body’s immune system can be modified to improve our ability to combat viral and bacterial infections.
The body’s immune system is designed to protect it from invading organisms and other pathogens. However, the immune system alone may not always be able to combat viral and bacterial infections, and antimicrobial therapies are implemented. A different approach would be to manipulate or affect immune system cells to control infections. Researchers at the Scripps Research Institute, La Jolla, CA have discovered that immune system molecules exist that can make people more vulnerable to bacterial infections, and that modifying expression or function of these immune molecules can enhance resistance to detrimental bacterial infections.
Interferons are immune system molecules that help inhibit viral replication. However, these same molecules are like a double-edged sword because they can also make it easier to be infected with harmful bacteria such as Listeria and Staphylococcus. The induction of the interferon-stimulated gene (ISG), USP18, impairs antibacterial immune responses normally mediated by tumor necrosis factor. The researchers found that deleting the USP18 gene in dendritic cells enhances the immune system’s antibacterial activity.
When USP18 is functional, it inhibits antibacterial tumor necrosis factor–alpha (TNF-alpha) signaling in laboratory mice infected with Listeria monocytogenes or Staphylococcus aureus. However, deleting USP18 in dendritic cells reduced bacterial levels in the mice, increasing their survival rate. Inhibiting the function of USP18 in dendritic cells promoted antibacterial activity of TNF-alpha subsequent to induction of reactive oxygen species that help destroy bacterial cells.
The approach of inhibiting USP18 function of immune cells is a means to modify the immune system to enhance its antibacterial function. Therefore, USP18 could serve as a therapeutic target in patients with severe bacterial infections. The approaches involving USP18 could also potentially enhance the antiviral activity of interferon signaling. The novel approach is distinct from the use of pharmacologic agents to directly affect viruses and bacterial cells that can become resistant to antimicrobial treatments. Instead, molecules within dendritic cells of the body’s immune system can be targeted to enhance the immune system’s capacity to kill or neutralize viruses and bacterial cells.
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Reference: 'Double agent' in the immune system may make us vulnerable to bacterial infections. (2018). ScienceDaily. Retrieved 6 November 2018, from https://www.sciencedaily.com/releases/2018/10/181004131836.htm