Biology subjects

Hen-Avivi, S.

Publications and source records attributed to Hen-Avivi, S..

3 recordsLinked to original sources

bioRxiv2026

Antibiotics drive immunometabolic rewiring of human immune responses

Antibiotics are routinely evaluated for their antimicrobial activity, potential host toxicity, and disruption of the microbiome. Certain antibiotics can also impact cell-intrinsic host processes, including evolutionarily conserved processes in the mitochondria. These raise the possibility that antibiotics can directly impact host immunity, which relies on mitochondrial function for their immunometabolic activation. However, the immunological consequences of most antibiotics in current use have not been systematically examined. Here, we performed a comprehensive analysis of the effects of clinically used antibiotics on activation of primary human immune cells. We uncovered an underappreciated antibiotic-specific modulation of immune function in healthy individuals and infectious disease patients. Focusing on the immunomodulatory antibiotic ciprofloxacin, we found altered mitochondrial gene expression across multiple immune populations, driving distinct, lineage-specific responses and heightened sensitivity of T-cells. Ciprofloxacin impaired primary human T-cell expansion and activation and altered mitochondrial function and metabolism. We further demonstrated immunomodulatory effects of selected antibiotics in response to inactivated bacteria and during live viral infection. Finally, to test the implications of our findings in vivo, we showed that immune activation is altered shortly after a single dose of antibiotic administration in mice. This work established a widespread impact of antibiotics on immune-cell function, and identified mitochondrial perturbation as one underlying mechanism, with implications for host-pathogen interactions and antimicrobial therapy.

immunology↗

bioRxiv2021

Cuticular Wax Composition is Essential for Plant Recovery Following Drought with Little Effect under Optimal Conditions

Despite decades of extensive study, the role of cuticular lipids in sustaining plant fitness is far from being understood. To answer this fundamental question, we employed genome editing in tree tobacco (Nicotiana glauca) plants and generated mutations in 16 different cuticular lipids-related genes. We chose tree tobacco due to the abundant, yet simply composed epicuticular waxes deposited on its surface. Five out of 9 different mutants that displayed a cuticular lipids-related phenotype were selected for in depth analysis. They had either reduced total wax load or complete deficiency in certain wax components. This led to substantial modification in surface wax crystal structure and to elevated cuticular water loss. Remarkably, under non-stressed conditions, mutant plants with altered wax composition did not display elevated transpiration or reduced growth. However, once exposed to drought, plants lacking alkanes were not able to strongly reduce their transpiration, leading to leaf death and impaired recovery upon resuscitation, and even to stem cracking, a phenomenon typically found in trees experiencing drought stress. In contrast, plants deficient in fatty alcohols exhibited an opposite response, having reduced cuticular water loss and rapid recovery following drought. This differential response was part of a larger trend, of no common phenotype connecting plants with a glossy appearance. We conclude that alkanes are essential under drought response and much less under normal non-stressed conditions, enabling plants to seal their cuticle upon stomatal closure, reducing leaf death and facilitating a speedy recovery.

plant biology↗

bioRxiv2021

scRNA-seq Reveals A Macrophage Subset That Provides A Splenic Replication Niche For Intracellular Salmonella

Interactions between intracellular bacteria and mononuclear phagocytes give rise to diverse cellular phenotypes that may determine the outcome of infection. Recent advances in single cell RNA-seq (scRNA-seq) have identified multiple subsets within the mononuclear population defined by unique molecular features, but the implications to their function during infection is unknown. Here, we applied high resolution kinetic analysis using microscopy, flow cytometry and scRNA-seq to survey the mononuclear niche of intracellular Salmonella Typhimurium (S.Tm) during early systemic infection in mice. We describe an eclipse like growth kinetics in the spleen, with a first phase of bacterial control mediated by tissue resident red pulp macrophages. A second phase involved bacterial growth mediated by intracellular replication within a macrophage population we termed CD9 macrophages, that originate from non-classical monocytes. Nr4a1e2-/- mice, specifically depleted of non-classical monocytes but not other mononuclear cells, are more resistant to S.Tm infection. Our study underscores a cell-type specific host-pathogen interaction that determines early infection growth dynamics and has implications to the infection outcome of the entire organism.

immunology↗