New mechanism on how immune cells sacrifice themselves to protect us from invading bacteria

New mechanism on how immune cells sacrifice themselves to protect us from invading bacteria

The same bacteria and viruses don't hit everyone with the same intensity. Some people get really sick, others less so. Some folks don't get sick at all. Why? What's really going on in the body when viruses and bacteria sneak in the back door and gear up for a full-on party?

The researchers have made a new discovery about what happens in the body when bacteria like Yersinia and Salmonella are at peak activity. This information could come in handy, not only because Yersinia still exists and because antibiotic resistance is a growing problem, but because the new knowledge can be transferred to help understand other diseases. Their finding has been published in the journal Science magazine.

It turns out that immune cells are so dedicated to their jobs that they explode themselves to release proteins that fight invading bacteria and resulting damage. The explosion does not go unnoticed and warns the other immune cells. The immune cells sacrifice themselves to let the other cells know what is going on. The process is so explosive that it is called pyroptosis.

What happens is that the immune cell forms small pores on its surface. This causes water to flow into the cell, which then swells until it bursts. When the cell explodes, it also releases substances that inhibit the invading bacteria from growing and that alert the other cells. Pretty effective, right?

Sneaky Yersinia knows all this, and tries to camouflage itself and secretes an antidote. The researchers figured out that the body knows that Yersinia disguises itself. At this point, the action starts to get really involved, but the article in Science explains that the immune cells initiate a backup mechanism that is triggered in a way not previously understood.

The activation of certain pattern-recognition receptors by pathogen-associated molecular patterns results in the formation of inflammasome complexes. Inflammasome complexes can initiate both the maturation of inflammatory cytokines and pyroptotic cell death via the caspase-mediated cleavage of gasdermin D (GSDMD).
As of now, the only known regulators of GSDMD in macrophages are caspase-1 and caspase-11. Researchers report an additional pathway controlling GSDMD processing. YopJ, an effector molecule produced by Yersinia (the causative agent of plague), inhibits TAK1–IκB kinase signaling. This, in turn, results in caspase-8–directed cleavage of GSDMD, pyroptosis, and the release of interleukin 1β (IL-1β) and IL-18.
Thus, in the arms race between host and pathogen, the host recognizes signaling disturbances as pathogenic and counters with inflammation and cell death.

"These findings show us complicated mechanisms that occur in the immune system to counter infection, but they may also apply to other diseases. Some of the same phenomena can happen in diseases that cause inflammation in the body in general, such as food poisoning or Alzheimer's disease. So these findings can also increase our understanding of inflammation, which happens in most diseases as changes occur in the body," says the author.