How special proteins help immune system fight infections

Three SWI/SNF protein complex variants, cBAF, ncBAF, and PBAF, gather around a campfire roasting marshmallows, with sashes symbolizing their different but cooperative identities. Together, they coordinate macrophage activity and control inflammation, represented by the fire. Credit: Salk Institute.

Our immune system is a powerful defender against bacteria, parasites, and viruses.

At the forefront of this defense are cells called macrophages, which are essential for identifying invaders and guiding the immune response.

Researchers at the Salk Institute have uncovered how these macrophages mount a coordinated and specific response to different threats.

Their findings were published in the journal Immunity on June 5, 2024.

Macrophages need the help of three versions of a protein complex called SWI/SNF to activate properly.

These versions are named cBAF, ncBAF, and PBAF. Although scientists knew these proteins had slightly different structures, the new research reveals that these differences significantly affect how macrophages respond to invaders.

Each version of the SWI/SNF protein complex plays a unique role in starting the macrophage response and regulating inflammation.

This discovery could lead to new treatments for conditions like sepsis, cytokine storm, and COVID-19, where inflammation is a major problem.

“Macrophages are our first line of defense and the recruiters for other immune cells, so understanding how they work is key to understanding our immune response,” says Diana Hargreaves, the senior author of the study and an associate professor at Salk.

“If we can figure out how macrophages tailor their responses to a given immune signal, we’ll have a better idea of how we can therapeutically target them to create desirable immune system behaviors.”

Macrophages are the first cells to sense an intruder in the body. They must correctly identify the invader and direct the rest of the immune system on how to respond. To do this, macrophages rely on precise internal signaling.

Inside each macrophage is a set of instructions encoded in DNA. This DNA is wrapped around proteins called histones and then wound into a 3D structure known as chromatin. Changes to histones and chromatin can reveal or hide parts of the DNA, affecting the cell’s behavior.

The SWI/SNF protein complex is known to make these changes, but it was unclear whether each version of SWI/SNF did this in a unique way. To learn more, researchers observed how macrophages in mice responded to bacterial infections and studied the differences among cBAF, ncBAF, and PBAF.

“We found the SWI/SNF variants each serve a unique, important purpose in reorganizing chromatin across the genome and enabling macrophage inflammatory responses,” says Jingwen Liao, a graduate student in Hargreaves’ lab and the first author of the study. “This is a major leap in our understanding of how immune systems respond with such a high level of specificity.”

By revealing these new mechanisms, the team has opened the door to developing therapies that can better control inflammation and improve our immune responses.

If you care about health, please read studies that vitamin D can help reduce inflammation, and vitamin K could lower your heart disease risk by a third.

For more health information, please see recent studies about new way to halt excessive inflammation, and results showing foods that could cause inflammation.