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Caught in an online: Study reveals that immune cells cooperate to lure and kill micro organism

Scanning electromicrograph of Staphylococcus aureus micro organism. Credit: NIAID

Like a spider trapping its prey, our immune system cells cooperate to seize and “eat” micro organism.

The newly recognized antibacterial mechanism, reported Sept. 10 in Science Advances, might encourage novel methods for combating Staphylococcus aureus (staph) and different extracellular bacterial pathogens.

It was recognized that neutrophils—first responder immune cells that migrate to websites of infection—can self-destruct and launch their protein and DNA contents to generate neutrophil extracellular traps (NETs). Now, Vanderbilt researchers led by postdoctoral fellow Andrew Monteith, Ph.D., have found that NETs increase the bacterial killing energy of one other kind of immune cell: macrophages.

“Neutrophils produce the spider webs that immobilize the bacteria, and macrophages are the spiders that engulf and kill the bacteria,” mentioned Eric Skaar, Ph.D., MPH, Ernest W. Goodpasture Professor of Pathology, Microbiology and Immunology and director of the Vanderbilt Institute for Infection, Immunology and Inflammation.

Staph micro organism—significantly antibiotic-resistant kinds—are a number one reason for hospital-acquired infections, infectious coronary heart illness and pus-forming pores and skin and mushy tissue infections.

Neutrophils and macrophages are each phagocytic cells recognized for ingesting micro organism and producing antimicrobial peptides, reactive oxygen species and different enzymes to struggle an infection. NET technology (NETosis), considered a type of programmed cell loss of life, is a extra not too long ago found neutrophil antibacterial technique, Skaar mentioned. The launched neutrophil DNA creates a sticky lure that can be studded with antimicrobial peptides.

Monteith and colleagues used neutrophils that bear elevated NETosis in animal and in vitro mannequin techniques to review the organic operate of NETs. They discovered that elevated NETosis didn’t present a killing benefit to neutrophils in isolation. But when macrophages have been current, NET formation enhanced macrophage antibacterial exercise by rising phagocytosis—of staph micro organism caught within the NETs together with neutrophil antimicrobial peptides.

“The macrophages end up with not only their own antibacterial arsenal, but also the neutrophils’ antibacterial arsenal, all in the same compartment killing the bacteria,” Skaar mentioned.

Increased NETosis additionally boosted macrophage killing of different bacterial pathogens together with Streptococcus pneumoniae and Pseudomonas aeruginosa. The findings recommend that neutrophil/NET-macrophage cooperation is a broadly used immune protection mechanism.

The researchers additionally confirmed that elimination of a staph nuclease enzyme that cuts DNA makes the micro organism much more delicate to NET-macrophage killing.

“It seems as if extracellular pathogens like staph have evolved secreted nucleases so they can cut their way out of these NETs—chop off the spider web and escape,” Skaar mentioned.

Blocking the nuclease would make the pathogens extra prone to NET-mediated killing and could also be a great antibacterial therapy technique. This kind of “anti-virulence” method would enable phagocytic and different immune cells to do their jobs and kill the micro organism, Skaar mentioned.

“Scientists are excited about the idea of anti-virulence strategies, because we know a lot about bacterial virulence mechanisms and can come up with creative ways to inhibit them,” he mentioned. Current pharmaceutical efforts, nevertheless, deal with medication that immediately kill micro organism relatively than blunting their virulence.

Monteith, Skaar and colleagues are persevering with to discover questions of NETosis, together with how and when neutrophils go for this type of cell loss of life. They are additionally thinking about how individual differences in NETosis—maybe due to genetic variation or illness states—have an effect on an infection. In individuals with sure autoimmune circumstances, for instance, decreased NETosis might enhance susceptibility to staph infections.

Other authors of the Science Advances paper embody Jeanette Miller, Noel Maxwell, and Walter Chazin, Ph.D.

Study shows male-female differences in immune cell function

More info:
Neutrophil extracellular traps improve macrophage killing of bacterial pathogens, Science Advances (2021). DOI: 10.1126/sciadv.abj2101

Caught in an online: Study reveals that immune cells cooperate to lure and kill micro organism (2021, September 10)
retrieved 10 September 2021
from https://phys.org/news/2021-09-caught-web-reveals-immune-cells.html

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