The discovery of sorting nexin 5 provides insight into how the body signals infection and manages tissue damage.
RT’s Three Key Takeaways:
- Immune Signaling: Researchers identified that sorting nexin 5 (SNX5) is essential for alerting the body to infection through the major histocompatibility complex (MHC) class II antigen presentation process.
- Inflammation Management: The study found that a lack of SNX5 results in excessive lung inflammation and higher mortality rates, even when bacterial levels remain the same as those with the protein.
- Clinical Implications: This discovery suggests that future healthcare approaches could focus on balancing protective immune responses with the prevention of tissue-damaging inflammation.
Researchers at UT Southwestern Medical Center identified a protein that helps the immune system respond to tuberculosis (TB) and control damaging inflammation. The findings, published in The Journal of Immunology, revealed that sorting nexin 5 (SNX5) plays a previously unknown role in helping immune cells alert the body to infection.
The study found that SNX5 is key to major histocompatibility complex (MHC) class II antigen presentation. During this process, immune cells display fragments of bacteria on their surface to signal other immune cells that an infection is present. Without SNX5, this communication system breaks down, leading to poorer activation of immune cells and increased lung inflammation during TB infection.
“The findings show that SNX5 is a previously unrecognized regulator of that process during Mycobacterium tuberculosis infection,” said Beatriz Dias, instructor of internal medicine in the division of infectious diseases and geographic medicine at UT Southwestern and lead author of the study, in a news release. “By linking a component of the cell’s protein-sorting machinery to antigen presentation and inflammation, this work provides new insight into how the immune system responds to tuberculosis.”
While SNX5 was already known to move materials within cells and assist in viral defenses, its role in bacterial infections was previously unclear. To investigate, researchers used mouse models and found that those lacking SNX5 experienced higher mortality after TB infection than mice with normal levels of the protein. Both groups carried similar amounts of TB bacteria, but mice without SNX5 developed significantly more lung inflammation, which can damage tissue and contribute to worse outcomes.
“This suggests the defect lies not in controlling the pathogen itself but in the body’s ability to tolerate infection and limit tissue damage,” said Dias in a news release.
The study suggests that SNX5 helps the body strike a balance between mounting a protective immune response and preventing excessive inflammation that can damage healthy tissue.
“A better understanding of these pathways may ultimately help identify new approaches to reduce harmful inflammation while preserving protective immune responses during infection,” said Michael Shiloh, professor of internal medicine and microbiology at UT Southwestern, in a news release.
Shiloh noted that the project was inspired by his collaboration with the late Beth Levine, whose work in autophagy, membrane trafficking, and host defense helped shape the study’s direction.
