How rod-shaped particles might distract an out-of-control COVID immune response

June 10, 2020

A long-ignored white blood cell may be central to the immune system overreaction that is the most common cause of death for COVID-19 patients--and University of Michigan researchers found that rod-shaped particles can take them out of circulation.

The No. 1 cause of death for COVID-19 patients echoes the way the 1918 influenza pandemic killed: their lungs fill with fluid and they essentially drown. This is called acute respiratory distress syndrome. But a new way of drawing immune cells out of the lungs might be able to prevent this outcome. This research is among the essential projects at U-M that have continued through the pandemic uninterrupted.

ARDS is a manifestation of a condition known as cytokine storm, in which the immune system overreacts and begins attacking the person's own organs. In ARDS, out-of-control white blood cells break down lung tissue and cause fluid to build up. Helping to lead the charge is a type of white blood cell called the neutrophil, which makes up 60% to 70% of intruder-eating "phagocyte" cells in humans.

"They're like the Coast Guard--their main job is to make sure your boundaries aren't breached," said Lola Eniola-Adefeso, University Diversity and Social Transformation Professor and a professor of chemical engineering, who led the research.

Neutrophils aren't specialized, which enables them to respond to many threats, she explained. But sometimes, that lack of specialization means they don't know when to quit.

"As long as there's cues, neutrophils keep acting. In some instances, the feedback loop is broken, and that turns what is meant to be a good response into a bad response," Eniola-Adefeso said.

One of their actions is to emit signaling molecules called cytokines that tell cells to break down barriers and let blood and fluid into a problem site. When that response turns bad, the neutrophils need to be stopped so that other cells can step in and repair the damage.

Previously, Eniola-Adefeso's group showed that plastic microparticles injected into the blood of mice could distract neutrophils, diverting them away from areas of severe inflammation in their lungs. The neutrophils would grab the particle and head to the liver to dispose of it. Microplastics used in this way eased ARDS in mice.

But any type of phagocyte might take up a sphere, which means a sphere-based therapy is likely to affect other parts of the immune response. However, it was already known that other phagocytes aren't fond of rod-shaped particles. Eniola-Adefeso said they "get lazy" with the long wrapping process around a rod.

"We asked, do neutrophils also have a disdain for eating rods?" she said. "We found the complete opposite. They actually have a preference for eating rods."

And that preference is useful for targeting neutrophils and leaving other white blood cells to do their jobs. They found that when they offered rods to different phagocytes, 80% of the neutrophils ate them, whereas only 5% to 10% of other phagocytes did. The comparisons included macrophages, another cell that eats intruders, and dendritic cells, which capture intruders and then show the other immune cells what to look for.

The team is currently exploring whether neutrophil-distracting particles can be made from medications rather than plastic. Eniola-Adefeso is now working with the U-M Office of Technology Transfer to advance her delivery system toward clinical trials, in hopes that it may prove useful in the fight against COVID-19. U-M has applied for patent protection and has launched a start-up company, Asalyxa.

Eniola-Adefeso is also a professor of biomedical engineering and professor of macromolecular science and engineering.
The paper is titled, "Neutrophils preferentially phagocytose elongated particles--opportunity for selective targeting in acute inflammatory diseases," and is published in the journal Science Advances.

The research is funded by the Falk Medical Research Trust, the National Institutes of Health and the University of Michigan.

Lola Eniola-Adefeso


University of Michigan

Related Immune Response Articles from Brightsurf:

Boosting chickens' own immune response could curb disease
Broiler chicken producers the world over are all too familiar with coccidiosis, a parasite-borne intestinal disease that stalls growth and winnows flocks.

Cells sacrifice themselves to boost immune response to viruses
Whether flu or coronavirus, it can take several days for the body to ramp up an effective response to a viral infection.

Children's immune response more effective against COVID-19
Children and adults exhibit distinct immune system responses to infection by the virus that causes COVID-19, a finding that helps explain why COVID-19 outcomes tend to be much worse in adults, researchers from Yale and Albert Einstein College of Medicine report Sept.

Which immune response could cause a vaccine against COVID-19?
Immune reactions caused by vaccination can help protect the organism, or sometimes may aggravate the condition.

Obesity may alter immune system response to COVID-19
Obesity may cause a hyperactive immune system response to COVID-19 infection that makes it difficult to fight off the virus, according to a new manuscript published in the Endocrine Society's journal, Endocrinology.

Immune response to Sars-Cov-2 following organ transplantation
Even patients with suppressed immune systems can achieve a strong immune response to Sars-Cov-2.

'Relaxed' T cells critical to immune response
Rice University researchers model the role of relaxation time as T cells bind to invaders or imposters, and how their ability to differentiate between the two triggers the body's immune system.

A novel mechanism that triggers a cellular immune response
Researchers at Baylor College of Medicine present comprehensive evidence that supports a novel trigger for a cell-mediated response and propose a mechanism for its action.

Platelets exacerbate immune response
Platelets not only play a key role in blood clotting, but can also significantly intensify inflammatory processes.

How to boost immune response to vaccines in older people
Identifying interventions that improve vaccine efficacy in older persons is vital to deliver healthy ageing for an ageing population.

Read More: Immune Response News and Immune Response Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to