04 August 2026
“Kill switch” for scavenger cells
A study from the NUCLEATE labs of Vogel and Westermann, in collaboration with researchers at the University of Marburg, was published in PNAS
Macrophages are a key component of the human immune system and help the body fight off infections by engulfing and “digesting” invading pathogens. However, some intracellular pathogens such as Salmonella can outwit these “scavenger cells” and even multiply inside them. Researchers have now identified a factor that helps macrophages balance self-preservation and effective pathogen clearance: a long non-coding RNA (lncRNA).
The findings open up new perspectives at the intersection of RNA biology, immunity, and infection research. Future studies will explore in greater detail how RNA-protein interactions shape inflammatory responses and host-pathogen dynamics. More broadly, the work highlights the emerging role of non-coding RNAs as important regulators of immune cell function and the immune response.
Original Publication
A human-specific long noncoding RNA regulator of antigen-presenting cell viability and antimicrobial defense.
Proc Natl Acad Sci U S A. · 2026
Show abstract
Macrophages are essential for both, to clear pathogens and preserve tissue homeostasis, yet the molecular regulators of this equilibrium remain incompletely defined. Here, we identify SAILR (survival associated immune-regulatory RNA), a primate-specific long noncoding RNA (lncRNA), as a critical modulator of macrophage viability under infection conditions. SAILR is induced during monocyte-to-macrophage differentiation, but rapidly downregulated upon bacterial challenge in a nuclear factor kappa B (NF-κB) dependent manner. In both naïve and immune-activated macrophages, SAILR dampens the expression of adhesion, phagocytosis, and invasion factors, which include SIGLEC1 and MMP7. During infection with Typhimurium, depletion of SAILR sensitizes macrophages to apoptosis, resulting in loss of intracellular replication niches and reduced bacterial recovery. Conversely, enforced SAILR expression promotes macrophage survival and increases intracellular pathogen burden. Mechanistically, SAILR interacts with the antiapoptotic adaptor protein 14-3-3β to support macrophage survival. Notably, downregulation of SAILR is mirrored in circulating immune cells from patients with severe COVID-19 and sepsis. Together, our findings position SAILR as a central regulator in linking macrophage survival to host-pathogen interaction and disease pathophysiology.