Biology subjects

Torne, J.

Publications and source records attributed to Torne, J..

3 recordsLinked to original sources

bioRxiv2025

NK cells undergo transcriptional and functional reprogramming following Streptococcus pneumoniae infection

Natural Killer (NK) cells are cytotoxic lymphocytes and key mediators of innate immunity, essential for combating viral infections and cancer. Notably, they exhibit immunological memory, generating a stronger response upon re-exposure to the same stimulus. While NK cell memory holds promise for infection control, its role in bacterial infections remains poorly understood. Previously, we demonstrated that Streptococcus pneumoniae induces long-term, specific, and protective NK cell memory. In this study, we performed single-cell RNA-seq to uncover how NK cells respond to S. pneumoniae infection. Our findings reveal that challenged Memory (cMemory) NK cells undergo transcriptional reprogramming following S. pneumoniae infection and have a differential transcriptional response upon reinfection. In addition, we identified distinct cMemory NK cell subpopulations, with responding cMemory NK cells displaying a general enhanced activation, proliferation, and cytotoxic activity. These findings support a novel role for NK cells in the context of bacterial infections, thereby opening avenues for harnessing the potential of innate immune memory for therapeutic applications.

immunology↗

bioRxiv2023

Streptococcus pneumoniae drives specific and lasting Natural Killer cell memory

NK cells are important mediators of innate immunity and play an essential role for host protection against infection, although their responses to bacteria are poorly understood. Recently NK cells were shown to display memory properties, as characterized by an epigenetic signature leading to a stronger secondary response. Although NK cell memory could be a promising mechanism to fight against infection, it has not been described upon bacterial infection. Here, we reveal that NK cells develop specific and long-term memory following sub-lethal infection with the extracellular pathogen Streptococcus pneumoniae. Memory NK cells display intrinsic sensing and response to bacteria in vitro, in a manner that is enhanced post-bacterial infection. In addition, their transfer into naive mice confer protection from lethal infection for at least 12 weeks. Interestingly, NK cells display enhanced cytotoxic molecule production upon secondary stimulation and their protective role is dependent on Perforin and independent of IFN{gamma}. Thus, our study identifies a new role for NK cells during bacterial infection, opening the possibility to harness innate immune memory for therapeutic purposes.

microbiology↗

bioRxiv2019

Two distinct HIRA-dependent pathways handle H3.3 de novo deposition and recycling during transcription

The packaging of DNA into nucleosomes represents a challenge for transcription. Nucleosome disruption and histone eviction enables RNA Polymerase II progression through DNA, a process that compromises chromatin integrity and the maintenance of epigenetic information. Here, we used the imaging SNAP-tag system to distinguish new and old histones and monitor chromatin re-assembly coupled to transcription in cells. First, we uncovered a loss of both old variants H3.1 and H3.3 that depends on transcriptional activity, with a major effect on H3.3. Focusing on transcriptionally active domains, we revealed a local enrichment in H3.3 with dynamics involving both new H3.3 incorporation and old H3.3 retention. Mechanistically, we demonstrate that the HIRA chaperone is critical to handle both new and old H3.3, and showed that this implicates different pathways. The de novo H3.3 deposition depends strictly on HIRA trimerization as well as its partner UBN1 while ASF1 interaction with HIRA can be bypassed. In contrast, the recycling of H3.3 requires HIRA but proceeds independently of UBN1 or HIRA trimerization and shows an absolute dependency on ASF1-HIRA interaction. Therefore, we propose a model where HIRA can coordinate these distinct pathways for old H3.3 recycling and new H3.3 deposition during transcription to fine-tune chromatin states.

cell biology↗