Mitochondria have primarily been known as the energy-producing components of cells. But scientists are increasingly discovering that these small organelles do much more than just power cells. They are also involved in immune functions such as controlling inflammation, regulating cell death and responding to infections.
Research from my colleagues and I revealed that mitochondria play another key role in your immune response: sensing bacterial activity and helping neutrophils, a type of white blood cell, trap and kill them.
For the past 16 years, my research has focused on understanding the decisions immune cells make during infection and how the breakdown of these decision-making processes cause disease. My lab’s recent findings shed light on why people with autoimmune diseases such as lupus may struggle to fight infections, revealing a potential link between dysfunctional mitochondria and weakened immune defenses.
Mitochondria do so much more than just produce energy.
OpenStax, CC BY-SA
The immune system’s secret weapons
Neutrophils are the most abundant type of immune cell and serve as the immune system’s first responders. One of their key defense mechanisms is releasing neutrophil extracellular traps, or NETs – weblike structures composed of DNA and antimicrobial proteins. These sticky NETs trap and neutralize invading microbes, preventing their spread in the body.
Until recently, scientists believed that NET formation was primarily triggered by cellular stress and damage. However, our study found that mitochondria can detect a specific bacterial byproduct – lactate – and use that signal to initiate NET formation.
Lactate is commonly associated with muscle fatigue in people. But in the context of bacterial infections, it plays a different role. Many bacteria release lactate as part of their own energy production. My team found that once bacteria are engulfed by a compartment of the cell called the phagosome, neutrophils can sense the presence of this lactate.
Inside the phagosome, this lactate communicates to the neutrophil that bacteria are present and that the antibacterial processes are not sufficient to kill these pathogens. When the mitochondria in neutrophil cells detect this lactate, they start signaling for the cell to get rid of the NETs that have entrapped bacteria. Once the bacteria are released outside the cell, other immune cells can kill them.
Here, a neutrophil engulfs MRSA bacteria (green).
When we blocked the mitochondria’s ability to sense lactate, neutrophils failed to produce NETs effectively. This meant bacteria were more likely to escape capture and proliferate, showing how crucial this mechanism is to immune defense. This process highlights an intricate dialogue between the bacteria’s metabolism and the host cell’s energy machinery.
What makes this finding surprising is that…
