Biology subjects

Battini, J.-L.

Publications and source records attributed to Battini, J.-L..

3 recordsLinked to original sources

bioRxiv2025

The phosphate exporter XPR1 regulates a gasdermin D-independent mature IL-1β secretion pathway in LPS-stimulated human monocytic cells

The inflammatory cytokine interleukin (IL)-1{beta} is a leaderless protein that is not secreted via the classical endoplasmic reticulum-Golgi pathway but instead is secreted during pyroptosis, a form of caspase-dependent inflammatory cell death mediated by gasdermin D (GSDMD) cleavage and pore formation at the plasma membrane. However, human monocytes can secrete IL-1{beta} in the absence of cell death, and the contribution of GSDMD in this secretory pathway is not established. Here, we identify two mechanisms of mature IL-1{beta} secretion by living human monocytic cells: a rapid, GSDMD-dependent pathway and a slower, GSDMD-independent pathway. Using a CRISPR-Cas9 loss-of-function screen, we identified XPR1 (Xenotropic and Polytropic retrovirus Receptor 1) as a key regulator of the GSDMD-independent pathway. XPR1 is the only phosphate exporter identified in metazoans and has no previously described function in cytokine secretion. XPR1 invalidation in GSDMD-/- monocytic cells impaired IL-1{beta} secretion. We further show that this regulatory function requires cell-surface expression of XPR1 and is linked to its phosphate export activity. Our results reveal a previously undescribed mechanism of IL-1{beta} secretion by living human monocytic cells, independent of GSDMD and unexpectedly linked to phosphate homeostasis. Deciphering this pathway could lead to new therapeutic modalities for IL-1{beta}-driven inflammatory diseases.

immunology↗

bioRxiv2024

Human plasma metabolic environment favours HIV replication in primary CD4 T lymphocytes

Cellular metabolism supports all viral replication steps and the metabolic state of infected cells is therefore a key factor influencing viral infections. Human Immunodeficiency virus (HIV) remains latent in resting CD4 T lymphocytes but actively replicates in activated CD4 T cells due to enhanced energy metabolism. Here, using the recently developed Human Plasma-Like Medium (HPLM) that mimics physiological plasma concentration of metabolites, we investigated how this near-physiologic environment modulates HIV-1 infection in primary CD4 T cells. Compared to the conventional culture medium (RPMI), HPLM enhanced HIV-1 infection in CD4 T cells despite similar levels of cell activation, proliferation and expression of viral receptor. In contrast with previous studies in RPMI, HPLM increased infection while decreasing energy metabolism and affecting other non-energetic metabolic pathways. Adjusting levels of several metabolites in RPMI and HPLM, we uncovered that the amino acids balance rather than the energy metabolism favoured HIV-1 replication in this system. Overall, our study used near-physiological conditions to better define metabolic dependencies of viral infections and highlights previously overlooked non-energetic metabolism pathways important for HIV-1 infection.

microbiology↗

bioRxiv2021

A co-opted endogenous retroviral envelope promotes cell survival by controlling SLC31A1/CTR1-mediated copper transport and homeostasis

Copper is a critical element for eukaryotic life, involved in numerous cellular functions and in redox balance but it can be toxic in excess. Therefore, tight regulation of copper acquisition and homeostasis is essential for cell physiology and survival. Here, we identified a unique mechanism for cell survival involving the regulation of copper homeostasis by an endogenous retroviral (ERV) envelope glycoprotein called Refrex1. We show that extracellular copper sensing by cells increases Refrex1 expression, which in turn regulates copper acquisition through interaction with the main copper transporter SLC31A1/CTR1. Downmodulation of Refrex1 resulted in intracellular copper accumulation leading to ROS production and subsequent apoptosis, which could be reverted by copper chelator treatment. Our results demonstrate that Refrex1 has been co-opted for its ability to regulate copper entry through CTR1 interaction in order to limit copper excess for a proper redox balance, and suggests that other ERV may have similar metabolic functions among vertebrates.

microbiology↗