Thursday, 13 December 2018

A Pyroptosis Primer: Immune System Cells Burst to Protect Us

Pyroptosis is a protective behaviour of certain cells in our body. When the cells detect the presence of a pathogen, they swell and burst, releasing chemicals that attract immune system cells to the scene. In essence, the exploding cell sacrifices itself in order to help us. The behaviour often leads to the rapid destruction of bacteria or viruses that are causing an infection. Sometimes it creates problems for us in the form of inflammation, however.

Some typical cell organelles; the chromatin in the nucleus contains DNA and protein
Credit: Koswac, CC BY-SA 4.0 License


The Human Immune System

The human immune system is complex and extremely important. It protects us from the pathogens (microbes that can cause disease) that enter our body every day. Survival would be impossible if we had no immune system and might be in danger if the system didn't work properly, depending on the extent of the disruption.

The immune system consists of specific cells, chemicals, and reactions. The cells work on their own or in combination with others, forming a protective network to help us. Different types of immune cells behave in different ways.

Programmed Cell Death

Cells in the body sometimes self-destruct when the cell is no longer needed or when the cell’s normal activity is seriously compromised. The process is known as programmed cell death. It’s “programmed” because the activities that cause the destruction originate in the cell’s components instead of from a factor located outside the cell or from an organism that has infected the cell. The destruction may be the cell’s response to an internal infection, however

Pyroptosis is one form of programmed cell death. Other forms exist, but pyroptosis is unique because it depends on an enzyme called caspase-1. One cause of the behaviour is a microbe infection. Pyroptosis triggers inflammation in the body as it operates. The inflammatory response is normally helpful for us. Blood, fluid, specific chemicals, and immune system cells flood the area, destroying microbes and repairing damaged tissue. As long as the inflammation subsides after these jobs have been done, it’s helpful. If inflammation is chronic (long-lasting), however, it can be harmful.

Though this article describes pyroptosis caused by pathogens, the process is also triggered by damage to cells resulting from a heart attack, a stroke, or cancer.

A Basic Overview of Pyroptosis

Like some other aspects of the immune system, pyroptosis is a complex process that isn’t completely understood. The process is sometimes referred to as caspase-1 dependent cell death because the chemical is responsible for the death of the cell. The following steps are known to be important in the process.

  • Toll-like receptors (TLRs) in a cell "recognize" molecular patterns on or in a pathogen by binding to them.
  • NOD-like receptors (NLRs) in the cell recognize toxic chemicals released by the pathogen.
  • An inflammasome is then made inside the inside the cell. An inflammasome is a complex of proteins that triggers the inflammatory response. In pyroptosis, it works by activating an enzyme called caspase-1, as shown in the illustration below.
  • Caspase-1 controls the activation and secretion of inflammatory cytokines. Cytokines are signaling proteins. They act as chemical messengers that trigger actions in other cells in the body. The cytokines released by the cell undergoing self-destruction trigger the activity of  immune system cells and result in inflammation in the area.
  • Caspase-1 also causes the creation of pores in the cell membrane. The pores allow fluid from the environment to flow into the cell, causing it to increase in size and eventually burst. The process is known as lysis.
  • Yet another effect of caspase-1 is that it causes DNA molecules to fragment. DNA, or deoxyribonucleic acid, is our genetic material.
The term pyroptosis (from the Greek ‘pyro’, relating to fire or fever, and ‘ptosis’, meaning a falling, is used to described the inherently inflammatory process of caspase 1-dependent programmed cell death. Quotation from Bergsbaken, Fink, and Cookson, Nature Reviews Microbiology 


A representation of an inflammasome that activates caspase-1; the pattern at the top of the illustration is the cell membrane
Credit: Haitao Guo, CC BY-SA 4.0 License


A Beneficial and Potentially Harmful Behaviour


Pyroptosis can certainly be very helpful in fighting microbes. Since it triggers inflammation, however, it’s also potentially harmful. Excessive or prolonged inflammation is undesirable and can cause or contribute to some major health problems.

It’s important that researchers continue to investigate pyroptosis and understand all of the steps involved in the process. In addition, inflammosomes need to be in investigated further. Hopefully this will eventually enable health practitioners to effectively treat infections without stimulating harmful consequences. In this age of antibiotic resistance in bacteria, finding new ways to treat bacterial infections is very important.

References

Immune cells sacrifice themselves to protect us from the MedicalXpress news service

Introduction to Pyroptosis: Educational material from ImmunoChemistry Technologies

Pyroptosis: Host Cell Death and Inflammation from Nature Reviews Microbiology (This articles contains some useful information but doesn't include the latest knowledge about pyroptosis.)