Biology subjects

Joly, M.

Publications and source records attributed to Joly, M..

5 recordsLinked to original sources

bioRxiv2026

Engineered T cells controlled by granulocyte colony-stimulating factor eradicate murine melanoma without lymphodepletion or interleukin-2

Tumour-infiltrating lymphocyte (TIL) therapy can be effective against metastatic melanoma, including immune checkpoint-resistant disease, but current protocols require lymphodepletion and high-dose interleukin-2 (IL-2), which can cause substantial toxicity. To overcome this limitation, we engineered a chimeric receptor, G2R, that generates an IL-2-like proliferative signal in response to granulocyte colony-stimulating factor (G-CSF), a well-tolerated cytokine widely used in oncology. Human T cells expressing G2R expanded in vitro in response to G-CSF in place of IL-2 or interleukin-15 (IL-15), and the three cytokines induced broadly similar intracellular signalling and cytokine secretion profiles. In immune-competent mice bearing established B16-F10 melanoma, adoptive transfer of G2R-expressing, tumour-reactive CD8+ T cells followed by systemic G-CSF treatment induced profound T cell expansion. This was accompanied by complete, durable tumour regression in over 75% of animals without the need for lymphodepletion, exogenous IL-2 or any other therapy. G-CSF treatment induced transient neutrophil expansion in peripheral blood but no increase in intratumoural neutrophils or macrophages. G2R-expressing memory T cells persisted long-term and could be re-expanded upon G-CSF re-treatment, enabling rejection of second tumour challenges. Thus, G-CSF can be repurposed to enable clinician-controlled anti-tumour T cell responses of profound magnitude, efficacy and durability, an approach that is readily translatable to humans.

immunology↗

bioRxiv2026

Temporal dynamics of grooming reciprocity in crested macaques: do social bonds affect exchange?

Primates maintain cooperative relationships largely through grooming reciprocity, yet studies disagree on the timescales over which grooming is returned. Part of this disagreement stems from statistical issues: inconsistent definitions of a reciprocation window, combined with the exclusion of unreciprocated grooming, leave the debate unresolved. We still do not know if primates exchange grooming within the short windows predicted by biological market theory or over much longer timescales. Whilst survival analysis can identify reciprocation windows objectively by retaining unreciprocated grooming as censored data, previous studies have applied it inconsistently. This inconsistency leaves the true time frames over which primates reciprocate grooming somewhat blurred. Here, we use a statistical approach that addresses these problems to examine grooming reciprocity in crested macaques (Macaca nigra), a socially tolerant macaque species. We applied survival analysis to identify each group's short-term reciprocation window without imposing arbitrary cut offs, and Bayesian survival models to test whether social bond strength and eigenvector centrality predicted reciprocation latency. Short-term reciprocation occurred rarely (29% of events in one group and 5% in the other); most reciprocation occurred over longer timescales than previous research commonly assumes. Stronger bonds predicted faster reciprocation; this finding suggests that crested macaques express social investment in valued partners through how promptly they return grooming, meaning that the timing of exchange carries information about relationship value. Eigenvector centrality showed no credible effect, though our small sample size and dense groups prevent us from interpreting this outcome more robustly. Substantial variation between dyads remained unexplained, pointing to partnerspecific properties we have yet to identify. These findings caution against assuming that reciprocity operates over short windows. They show that social predictors, such as bond strength, remain essential to understanding when primates return grooming. This work provides a baseline for testing whether grooming is exchanged for other social commodities, and for comparing reciprocation timescales across macaque species that differ in social tolerance.

animal behavior and cognition↗

bioRxiv2023

Clouds, oases for airborne microbes. Differential metagenomics/ metatranscriptomics analyses of cloudy and clear atmospheric situations

Bacteria cells and fungal spores can aerosolize and remain suspended in the atmosphere for several days, exposed to water limitation, oxidation, and lack of nutrients. Using comparative metagenomics/metatranscriptomics, we show that clouds are associated with the activation of numerous metabolic functions in airborne microorganisms, including fungal spore germination. The whole phenomenon mirrors the rapid recovery of microbial activity in soils after rewetting by rain, known as the "Birch effect". Insufficient nutrient resources in cloud droplets cause a famine that recycling cellular structures could alleviate. The recovery of metabolic activity by microorganisms in clouds could favor surface invasion upon deposition, but it may also compromise further survival upon cloud evaporation. In any case, clouds appear as floating biologically active aquatic systems. One-Sentence SummaryClouds activate metabolic processes in airborne microorganisms

ecology↗

bioRxiv2023

Experimental and methodological framework for the assessment of nucleic acids in airborne microorganisms

Studying airborne microorganisms is highly challenging due to ultra-low and spread biomass, and great spatial and temporal variabilities at short scales. Aeromicrobiology is still an emerging discipline of environmental microbiology, and some of the basic practices (replication, control of contaminants, etc) are not yet widely adopted, which potentially limits conclusions. Here we aim at evaluating the benefits of such practices in the study of the aeromicrobiome using molecular-based approaches, and recommend the following: (i) sample at high airflow rate, if possible into a fixative agent, in order to be able to capture specific situations ; (ii) replicate sampling and process samples individually to enable statistical analyses ; (iii) check for contaminants at different steps of the analytical process, and account for their potential stochasticity in sequence decontamination methods ; (iv) include internal references to verify qualitative and quantitative aspects of the data, and (v) eventually investigate multiple analytical procedures to identify potential impacts on the data. In our study, samples were collected at a remote mountain site using high-flow rate impingers collecting airborne material into nucleic acid preservation buffer. As high of [~]75% of the sequences were shared between independent triplicates, gathering 28 to 38% of the richness observed at the ASV level at a given sampling date, which also emphasizes spatial heterogeneity at short scale due to rare taxa. Thanks to replicates, daily variations in the diversity of bacteria could be distinguished statistically, and the inevitable presence of contaminating sequences in controls could be accounted for using established statistical methods. This work opens new perspectives and notably paves the way to untargeted molecular methods in the exploration of aeromicrobiomes composition and functioning. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/561683v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@48bddcorg.highwire.dtl.DTLVardef@1a8c3fforg.highwire.dtl.DTLVardef@dba98forg.highwire.dtl.DTLVardef@159055e_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2023

Glycolytic imprinting of monocytes impairs HIF1α-driven migration of dendritic cells in tuberculosis

During tuberculosis, migration of dendritic cells (DCs) from the site of infection to the draining lymph nodes is known to be impaired, hindering the rapid development of protective T-cell mediated immunity. However, the mechanisms involved in the delayed migration of DCs during tuberculosis (TB) are still poorly defined. Here, we found that infection of DCs with Mycobacterium tuberculosis (Mtb) triggers HIF-1-mediated aerobic glycolysis in a TLR2-dependent manner, and that this metabolic profile is essential for DC migration. In particular, the lactate dehydrogenase (LDH) inhibitor oxamate and the HIF-1 inhibitor PX-478 abrogated Mtb-induced DC migration in vitro to the lymphoid tissue-specific chemokine CCL21, and in vivo to lymph nodes in mice. Strikingly, we found that although monocytes from TB patients are inherently biased toward glycolysis metabolism, they differentiate into poorly glycolytic and poorly migratory DCs, compared with healthy subjects. Taken together, these data suggest that because of their preexisting glycolytic state, circulating monocytes from TB patients are refractory to differentiation into migratory DCs, which may explain the delayed migration of these cells during the disease and opens avenues for host-directed therapies for TB. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/535400v6_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@9c6849org.highwire.dtl.DTLVardef@82981dorg.highwire.dtl.DTLVardef@1d0b7faorg.highwire.dtl.DTLVardef@1deb76f_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗