Whenever there is a wound or infection, the body produces an inflammatory response. This is the body's first line of defence, and macrophages - cells of the innate immune system - play a key role: first, they help eliminate pathogens and other infectious agents, and then they trigger the mechanisms that repair the damage caused during the inflammatory process. Now, a study by the University of Barcelona, the findings of which have been published in the journal Cell Reports , has discovered that a protein called Polμ is essential to this repair process, as it enables macrophages to survive at the site of inflammation. According to the researchers, a deficiency of this protein could be the cause of certain autoinflammatory diseases, conditions in which the immune system is activated inappropriately, leading to chronic inflammation and tissue damage.
The study, conducted using animal models, was led by researchers Jorge Lloberas, Antonio Celada and Carlos Sebastián, all three members of the Immunology Section of the Department of Cell Biology, Physiology and Immunology at the Faculty of Biology, the Barcelona Science Park-UB (PCB-UB) and the Consolidated Research Group on Inflammation: Basic and Translational Research (InFlam-BaTra). Carlos Sebastián is also a member of the UB Institute of Biomedicine (IBUB) and is currently the principal investigator of the Metabolic Dynamics in Cancer Group.
Carlos Batlle-Recoder is the lead author of the study, which included the participation of the National Centre for Biotechnology (CNB-CSIC).
The collateral damage caused by defence mechanisms
When the innate immune system triggers the inflammatory response to an external threat, macrophages engulf the pathogens and produce large quantities of reactive oxygen species (ROS) to destroy them. However, ROS also have a harmful effect on the macrophages themselves, as they can induce DNA damage that may lead to the death of these defence cells and promote chronic inflammation.
Previous studies had demonstrated the importance of Polμ in lymphocyte development and its involvement in the repair of genetic damage, but until now, its role in macrophages and in the inflammatory response was unknown. The researchers have discovered this by analysing the protein's role in this process using animal models of skin inflammation and muscle injury. "Using mice lacking Polμ, we have been able to demonstrate, in both in vitro and in vivo experiments, that the two phases of the inflammatory response are defective in the absence of this polymerase," they explain.
