A human-specific long noncoding RNA regulator of antigen-presenting cell viability and antimicrobial defense

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 Salmonella 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.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2026-07-16
DOI
https://doi.org/10.1073/pnas.2520205123
Primary Topic
Immune cells in cancer
Type
article
Field-Weighted Citation Impact
0.00

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article

A human-specific long noncoding RNA regulator of antigen-presenting cell viability and antimicrobial defense

Leon N. Schulte, Evangelos J. Giamarellos‐Bourboulis, Uwe Linne, DiyaaElDin Ashour et al.
Proceedings of the National Academy of Sciences
Immune cells in cancer
article

A human-specific long noncoding RNA regulator of antigen-presenting cell viability and antimicrobial defense

Leon N. Schulte, Evangelos J. Giamarellos‐Bourboulis, Uwe Linne, DiyaaElDin Ashour, Elisabeth Mack, Nikolaos Antonakos, Jörg Vogel, Alexander J. Westermann, Thomas Herrmann, Bernd Schmeck, Sebastian Weis, Chrysanthi Skevaki, Sandra Wende, Eleni Florou, Alexandra Schock
article en

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 Salmonella 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.

Proceedings of the National Academy of SciencesVol. 123(29)
Philipps University of Marburg (DE), Schiller International University (FR), Johannes Gutenberg University Mainz (DE), Justus-Liebig-Universität Gießen (DE), National and Kapodistrian University of Athens (GR), Academy of Athens (GR), University of Würzburg (DE), Universitätsklinikum Gießen und Marburg (DE), University Medical Center of the Johannes Gutenberg University Mainz (DE), IONICS Mass Spectrometry (Canada) (CA), Helmholtz Centre for Infection Research (DE), Innovation Cluster (Canada) (CA), Helmholtz Institute for RNA-based Infection Research (DE), Universitätsklinikum Würzburg (DE), German Center for Lung Research (DE), Universities of Giessen and Marburg Lung Center (DE), Hellenic Society for the Study of Bone Metabolism (GR), Loewe Center for Synthetic Microbiology (DE), Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE), Friedrich Schiller University Jena (DE)
Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Bundesministerium für Gesundheit, Fritz Thyssen Stiftung, Hessisches Ministerium für Wissenschaft und Kunst
Openalex Percentile: Top 14%
Immune cells in cancer
DOIOpen Access PDFOpenAlex
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