Humans may never notice this superhero germ-fighting duo, yet they work wonders in the immune system. Spider-Man-like immune cells sling webs to seize invasive bacteria and keep supervillains restrained until Pac-Man-like cells come to gobble them up.#
Writer: Sara Maria Majernikova
Editor: Maddie Throssell
Artist: Eshka Chuck
A primary role of immune cells and proteins is to defend living organisms from invasions. Firstly, there are neutrophils, which make up more than half of our white blood cells. These cells are often the first to arrive at the infection scene and attack invaders by gobbling up the intruders or ‘inviting’ other immune cells to fight. However, occasionally neutrophils pull a Spider-Man maneuver, meaning they shoot sticky DNA webs and toxic proteins which ensnare pathogens and prevent them from spreading. Because neutrophils die when engaging in this process, researchers consider the webs a cellular version of suicide bombing. On the other hand, macrophages (white blood cells’ “munching” bacteria) are known for their ability to gobble up cellular debris and pathogens to thwart infection, being the “Pac-Man” of the immune system and forming the body’s first line of defence against invasion. They indiscriminately engulf and eat almost anything deemed a dangerous trespasser, whether it’s a bacterium or cellular debris from deceased tissue. In these cells’ ultimate superhero crossover, Spider-Man-like immune cells sling webs to capture and kill invasive bacteria in order to keep those supervillains restrained until Pac-Man-like cells come to gobble them up, according to new research by Monteith et al. .
In 2018, Zychlinsky and colleagues discovered neutrophil extracellular traps (NETs), which carry chemical red flags prompting macrophages to spark inflammation at an infection site, The Scientist reports. Conversely, Monteith et al. suggests that the two cell types also team up to launch coordinated attacks against invasive microbes. Skaar claims neutrophils cast their NETs to immobilize the “bad guys.” Then, macrophages swoop in and swallow the bugs whole, not unlike how Pac-Man devours ghosts. “While gobbling down its catch, the macrophage is actually taking this giant bite out of the NET,” Skaar informs. The antimicrobial proteins from the NET then mix with antimicrobial proteins already in the macrophage’s stomach, thus together, the two cell types degrade bacteria more effectively than either cell could alone. Due to low levels of antimicrobial proteins, Monteith‘s research team explored how neutrophils come into contact with staph bacteria and their mitochondria. They discovered that this contact generates harmful free radicals in the cell, which drives the cell to self-destruct and release its NETs more quickly than it would otherwise. This speedy NET casting boosts the ability of neutrophils and macrophages to clear staph from the body, as a germ-fighting duo.
In their recent mouse studies, researchers led by Monteith found that some neutrophils release their NETs quicker than others when chasing down staph bacteria. Specifically, a protein (called S100A9) dictates how quickly neutrophils sling their webs. Mice with low levels of this protein seem to survive better against methicillin-resistant S. aureus (MRSA), the team confirmed in a 2017 study published in the journal Cell Host & Microbe. The same held true when the team pitted the immune cells against Streptococcus pneumoniae and Pseudomonas aeruginosa, both of which can infect many organs in the body, including the lungs and brain. The research by Monteith et al. was conducted in mice and mouse cells, but it still may help to explain how neutrophils fight off infections in humans and why they sometimes fail. It turns out that these spidery cells may not work well in people with autoimmune conditions, such as lupus, making those individuals more susceptible to staph infections. When a staph infection first begins to take hold in the body, the ‘friendly neighbourhood neutrophils swoop in as first responders to help fight the Staphylococcus aureus bacteria, as senior author Skaar revealed to Live Science. These neutrophils have a secret weapon: they can self-destruct and eject a sticky web from their ruptured membranes. This web, named a NET, contains neutrophil DNA studded with proteins degrading bacteria.
According to Skaar, having research based only on mice is a major limitation. Additionally, people suffering from certain autoimmune conditions, such as lupus and rheumatoid arthritis, produce more of the S100A9 protein than people without these conditions. Thus, in theory, those neutrophils may release their NETs slower than average, Skaar informs. This could explain why these individuals are more susceptible to illness than the general population. However, researchers need to confirm their theory in humans. On top of exploring this potential link to autoimmune diseases, the team plans to study exactly why S100A9 influences the speed at which neutrophils deploy their sticky NETs. Scientists could then boost the web-slinging abilities of neutrophils, to supercharge their infection-fighting abilities.