Research has found that immune cells collaborate to prey on bacteria.

Microorganisms such as bacteria, fungi, and viruses are ubiquitous. Though tiny in size, they can sometimes pose a life‑threatening risk to humans. Nevertheless, in many cases, our bodies are able to fend off these microbial invaders or learn to coexist with them, thanks to the immune system’s critical role as a protective barrier. It goes without saying that in-depth investigation of the immune system’s specific mechanisms for combating microorganisms is of great significance for developing more effective antimicrobial therapies and drugs.

Just as spiders capture their prey, our immune cells work together to trap and “consume” bacteria. According to Medical Information Network, researchers at Vanderbilt University Medical Center have uncovered a novel antibacterial mechanism in immune cells, which could help develop new strategies to combat Staphylococcus aureus and other pathogens.

　　It is known that neutrophils—first‑line immune cells that migrate to sites of infection—can undergo programmed cell death and release their proteins and DNA, thereby forming neutrophil extracellular traps (NETs). In this study, researchers found that NETs can enhance the bactericidal capacity of another type of immune cell: macrophages.

　　“Neutrophils produce a ‘spiderweb’ that immobilizes bacteria, while macrophages act as the ‘spiders’ that engulf and kill the bacteria,” said Dr. Eric Sklar, one of the researchers.

　　Neutrophils and macrophages are both phagocytic cells that can engulf bacteria and produce antimicrobial peptides and other substances to combat infection. According to Skar, the formation of NETs is accompanied by neutrophil death—a process known as NETosis—which has recently been identified as an antimicrobial strategy employed by neutrophils. The DNA released during this process forms a sticky trapping network densely packed with antimicrobial peptides.

　　Researchers investigated the biological functions of NETs in animal and in vitro model systems. They found that, under conditions where macrophages were isolated, an increase in NETosis did not confer a killing advantage to neutrophils. However, in the presence of macrophages, both phagocytosis and neutrophil antimicrobial peptides were enhanced, and NET formation further boosted the antibacterial activity of macrophages.

　　Skar stated that macrophages ultimately possess not only their own antimicrobial arsenal but also that of neutrophils, and together they kill bacteria.

　　Increased NETosis also enhances the ability of macrophages to kill other bacterial pathogens, such as Streptococcus pneumoniae and Pseudomonas aeruginosa. The findings indicate that neutrophil–NET–macrophage cooperation represents a widely employed immune defense mechanism.

　　The study also shows that eliminating a DNA‑cleaving nuclease in Staphylococcus makes the bacteria more susceptible to killing by NETs and macrophages. This is because bacteria have evolved the ability to secrete nucleases, allowing them to “cut their way” out of the NETs—disrupting the “spiderweb” and escaping. Inhibiting this nuclease renders the bacteria more easily captured by NETs, representing a strategy to attenuate virulence and potentially enhancing the antimicrobial efficacy of phagocytes and other immune cells.

　　The Medical Information Network has found that, at present, drugs targeting antibacterial mechanisms are largely focused on directly killing bacteria rather than attenuating their virulence. This finding may offer new avenues for the development of novel antimicrobial agents.