Biology subjects

Jennings, L. K.

Publications and source records attributed to Jennings, L. K..

3 recordsLinked to original sources

bioRxiv2026

The breast tumor microenvironment exploits eosinophil plasticity to suppress their anti-tumor activity

Eosinophils recently emerged as mediators of anti-tumor immunity in immune checkpoint blockade (ICB) treated breast cancer patients. Yet, their role in the treatment-naive breast tumor microenvironment (TME) remains elusive. Here, we show that the breast TME shapes eosinophils into a less active state characterized by loss of Ly6C. While bone marrow and circulating eosinophils are Ly6C, this population progressively transitions into a Ly6C- state marked by reduced cytotoxicity and interferon (IFN) responsiveness during tumor progression. Further investigation of Ly6C uncovered previously unappreciated granularity of eosinophil differentiation in vitro, recapitulating the Ly6C to Ly6C- transition and associated functional loss observed in vivo. IFN stimulation partially restored the Ly6C phenotype ex vivo. Importantly, in ICB-treated tumors, Ly6C+ eosinophils positively correlated with increasing levels of IFNs, suggesting an additional mechanism by which IFNs contribute to effective ICB responses. We propose Ly6C as a key marker of eosinophil differentiation and activation, with the TME shaping eosinophils into a less cytotoxic Ly6C- state.

immunology↗

bioRxiv2022

Bacterial threat assessment of bacteriophage infection is mediated by intracellular polyamine accumulation and Gac/Rsm signaling

When eukaryotic cells are killed by pathogenic microorganisms, damage-associated and pathogen-associated signals are generated that alert other cells of nearby danger. Bacteria can detect the death of their kin; however, how bacteria make threat assessments of cellular injury is largely unexplored. Here we show that polyamines released by lysed bacteria serve as damage-associated molecules in Pseudomonas aeruginosa. In response to exogenous polyamines, Gac/Rsm and cyclic-di-GMP signaling is activated and intracellular polyamine levels increase. In the absence of a threat, polyamines are catabolized, and intracellular polyamines return to basal levels, but cells infected by bacteriophage increase and maintain intracellular polyamine levels, which inhibits phage replication. Phage species not inhibited by polyamines did not trigger polyamine accumulation by P. aeruginosa, suggesting polyamine accumulation and metabolism are targets in the phage-host arms-race. Our results suggest that like eukaryotic cells, bacteria can differentiate damage-associated and pathogen-associated signals to make threat assessments of cellular injury. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/486733v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@1f69334org.highwire.dtl.DTLVardef@13a4422org.highwire.dtl.DTLVardef@4f3edeorg.highwire.dtl.DTLVardef@a86c43_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2021

The depletion mechanism can actuate bacterial aggregation by self-produced exopolysaccharides and determine species distribution and composition in bacterial aggregates

Bacteria causing chronic infections are often found in cell aggregates suspended in polymer secretions, and aggregation may be a factor in infection persistence. One aggregation mechanism, called depletion aggregation, is driven by physical forces between bacteria and polymers. Here we investigated whether the depletion mechanism can actuate the aggregating effects of P. aeruginosa exopolysaccharides for suspended (i.e. not surface attached) bacteria, and how depletion affects bacterial inter-species interactions. We found cells overexpressing the exopolysaccharides Pel and Psl, but not alginate remained aggregated after depletion-mediating conditions were reversed. In co-culture, depletion aggregation had contrasting effects on P. aeruginosas interactions with coccus- and rod-shaped bacteria. Depletion caused S. aureus (cocci) and P. aeruginosa (rods) to segregate from each other, S. aureus to resist secreted P. aeruginosa antimicrobial factors, and the species to co-exist. In contrast, depletion aggregation caused P. aeruginosa and Burkholderia sp. to intermix, enhancing type VI secretion inhibition of Burkholderia by P. aeruginosa, leading to P. aeruginosa dominance. These results show that in addition to being a primary cause of aggregation in polymer-rich suspensions, physical forces inherent to the depletion mechanism can actuate the aggregating effects of self-produced exopolysaccharides and determine species distribution and composition of bacterial communities.

microbiology↗