NIAID Researchers Describe How Immune Cells Swarm to Injuries and Infections

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NIAID Researchers Describe How Immune Cells Swarm to Injuries and Infections

NIAID Researchers Describe How Immune Cells Swarm to Injuries and Infections

NIAID researchers have described how specialized immune cells called neutrophils form tight clusters at wounds or infected areas. These findings may potentially lead to the development of new strategies to promote or interfere with inflammatory immune responses. The investigators report their results in the May 26, 2013, online issue of Nature.

Background

Neutrophils are infection-fighting white blood cells that circulate in the bloodstream and look for signs of infection or injury, such as a cut on the skin. When these cells detect damage, they move into the body’s tissues and form tight, dense clusters—similar to an insect swarm—around the site of the injury. The swarming neutrophils kill and digest bacteria and help break down damaged tissue.
Neutrophils communicate with one another by sending and receiving various chemical signals. The neutrophil surface is covered with more than 30 receptors, each of which recognizes a different type of signal. While scientists have described how neutrophils exit blood vessels, little is known about how they communicate with each other after they have left the bloodstream and move to the site of infection or damage.

Results of Study

Tim Lämmermann, Ph.D., and Ronald Germain, M.D., Ph.D., of NIAID’s Laboratory of Systems Biology used an advanced microscope to observe neutrophil behavior in the skin of mice given small burns. The researchers recorded short videos of neutrophil swarming in normal mice and mice lacking various neutrophil proteins such as surface receptors. They also investigated neutrophil swarms in the lymph nodes of mice with a bacterial infection.
Together with their collaborators at NIH, the scientists found that neutrophils use a lipid (fat) called LTB4 to communicate with each other after the first few cells discover the wound or infection. This lipid helps guide the cells through the tissue and swarm at the site of damage. Integrins—molecules that control how cells stick to each other and to their surroundings—work with LTB4 and other chemicals to promote interactions among the neutrophils and seal wounds.

Significance

The team’s findings provide a detailed description of how neutrophils communicate with each other to move through tissues and form tight clusters at damaged or infected areas. Unraveling these events helps scientists better understand how inflammatory responses occur.

Next Steps

The researchers plan to investigate whether they can manipulate this network of communications to strengthen the immune response or to treat chronic inflammation.

Neutrophils (in red) accumulate within minutes at sites of local tissue injury (center). They then communicate with each other using lipid and other secreted mediators to form cellular "swarms." Their coordinated movement and exchange of signals then instructs other innate immune cells called macrophages and monocytes (in green) to surround the neutrophil cluster and form a tight wound seal. This 24-second video represents a two-hour recording.

Reference

Lämmermann T, Afonso PV, Angermann BR, Wang JM, Kastenmüller W, Parent CA, Germain RN. Neutrophil swarms require LTB4 and integrins at sites of cell death in vivo. Nature DOI: 10.1038/nature12175 (2013)
NIAID Laboratory of Systems Biology