Research led by Lancaster University has discovered that a class of antibiotics - fluoroquinolones - can directly alter the potential bacterial killing ability of one of our immune cells called the macrophage.
Our lungs must balance the essential acts of absorption of oxygen and release of carbon dioxide with the continuous risk of airborne pathogens. The lung therefore hosts a myriad of immune cells designed to protect us from these invaders, but these defences can still be overwhelmed resulting in life threatening infections.
Macrophages are key immune cells involved in monitoring barrier sites such as the lung and gut during infection and can produce noxious molecules which can kill bacteria as well as "eating" surrounding bacteria, termed "phagocytosis".
Like all cells, macrophages contain mitochondria which produce energy for cell function. It has been previously shown that our mitochondria have evolved from bacterial ancestry and retain many pathways that could still be targeted by antibiotics.
The new findings published in the journal "Discovery Immunology" demonstrate how fluoroquinolones directly stress, rather than kill, macrophage mitochondria altering their metabolism to a state which is beneficial for bacterial clearance.
Lead researcher Dr John Worthington from the Department of Biomedical and Life Science at Lancaster said: "Many previous observations have examined antibiotic use during bacterial infections where direct immune alterations could be missed. Examining multiple lung immune cell types during antibiotic treatment in the uninfected state, we noticed that macrophages had a higher level of an enzyme called inducible Nitric Oxide Synthase (iNOS), which makes the bacterial killing molecule nitric oxide. Interestingly, this only occurred in certain types of immune cells. We found that in both the gut and lung it was specific subsets of younger macrophages that were affected and not the long-lived populations."
Dr Alex Hardgrave, who is co-first author, said: "There are many factors which could be responsible for our initial observations in the lung and gut, so we grew macrophages in the lab and again observed increased iNOS expression and an improved ability of macrophages to phagocytose or swallow the bacteria, demonstrating a direct antibiotic macrophage effect".
Antibiotics are the main treatment for limiting serious complications in many bacterial lung infections, and act by inhibiting the growth or killing infective bacteria. However, antibiotic use can have many negative side effects such as also targeting our beneficial bacteria.
Dr Megan Dooley, co-first-author, said: "Previous side effects of fluoroquinolone use have demonstrated reduction in our essential microbiome, weight loss and tendon damage during long-term use possibly from mitochondrial damage. However, this study adds to the literature that antibiotics do have immunomodulatory properties that may have beneficial and detrimental effects that most people don't think about."
Dr Worthington added caution to the findings.
"The dual function of an antibiotic which directly kills bacteria and supports macrophage function to also target bacteria sounds like a perfect combination. Yet, uncontrolled inflammation can actually produce damage to our own tissues and therefore cause 'more bad than good'. However, adding this knowledge to our therapeutic options when choosing which antibiotic class to use would potentially allow us to select the most beneficial antibiotic for an individual patient's needs".
