Biology subjects

Gres, V.

Publications and source records attributed to Gres, V..

3 recordsLinked to original sources

bioRxiv2025

Mycobacterial infection uncovers plasticity of Kupffer cells

Bona fide Kupffer cells (KCs) are prenatally seeded and show unique functional and immunophenotypic features among tissue macrophages. They are considered as terminally differentiated, and adaptability in disease is attributed to recruited, monocyte-derived KCs. Here, we investigated the extent of KC plasticity and the impact of origin in mycobacterial infections that target macrophages and can persist for months. Fate-mapping combined with high-resolution imaging revealed the emergence of a unique, infection specific KC subset which downregulated the signature markers CLEC4F and VSIG4 ("KClow"). KClow were derived from bona fide KCs and located exclusively to granuloma cores. In contrast, monocyte-derived macrophages were contained at the granuloma borders and contributed to this tissue reaction. ATAC and single-cell RNA sequencing identified a specific signature of KClow with high antimycobacterial activity and specialization to a hypoxic microenvironment. Despite their fundamental deviation from the classical KC phenotype, KClow showed remarkable adaptability, and were capable to return to a homeostatic-like KC state. Accordingly, mycobacterial infections unmask KCs as highly plastic cells, capable of responding to extreme environmental changes.

immunology↗

bioRxiv2025

Sensory neurons shape macrophage identity via TGF-β signalling

Macrophages play integral roles in maintaining homeostasis and function in their tissues of residence. In the skin, prenatally seeded and highly specialized macrophages physically interact with sensory nerves and contribute to their regeneration after injury. However, mechanisms underlying the development and maintenance of this potentially lifelong commitment of macrophages to nociceptors remain largely elusive. Here, we found that infiltrating myeloid progenitor cells approached the sprouting axons of sensory nerves and gradually adopted a nerve-associated macrophage-like profile. This change in identity was steered and maintained by the immediate microenvironment, in particular TGF-{beta}, which was locally activated by the physical interaction with nerves and integrin-mediated cleavage. Following injury, TGF-{beta} driven specification of macrophages essentially supported nerve regeneration. Overall, we identified TGF-{beta} as a central mediator governing local imprinting and long-term specialization of macrophages in the skin, providing insights into the bidirectional communication between macrophages and sensory nerves.

immunology↗

bioRxiv2024

Dynamic role of monocytes and meningeal macrophages in bacterial meningoencephalitis

Macrophages in the meninges, especially in the dura mater sheathing the brain from the skull, are involved in the immune defense of the central nervous system (CNS). However, their site-specific origin and function, both in steady state and in bacterial CNS infections are incompletely understood. Using an intravenous model of streptococcal meningoencephalitis that mimics hematogenous dissemination in humans, we found that bacteria accumulated predominantly in the leptomeninges and dura, whereas invasion into the brain parenchyma was rare. However, monocyte infiltration into the leptomeninges and parenchyma strongly correlated with disease severity. In the dura, infection triggered activation and loss of resident macrophages, followed by rapid engraftment of inflammatory monocytes that transiently replenished the dural macrophage niche. Under homeostasis, dural monocytes were supplied independently of CCR2 from adjacent skull bone marrow. In infection, however, this local reservoir was rapidly exhausted, and the markedly increased demand for monocytes required mobilization from peripheral bone marrow sources, revealing context-dependent heterogeneity in monocyte origin. Infection also reshaped ontogeny of this differential monocyte output, with an increase in Monocyte-Dendritic Cell Progenitor - derived monocytes (MDP-Mo). MDP-Mo exhibited enhanced MHC-II expression and persisted in the brain during the resolution phase together with CD4 T cells, suggesting a role in antigen presentation after bacterial clearance. Together, these findings reveal a highly dynamic and compartment-specific remodeling of monocyte ontogeny, recruitment, and differentiation across CNS borders during bacterial meningoencephalitis. These mechanisms may offer opportunities for therapeutic interventions in the future. One Sentence SummaryStreptococcal meningoencephalitis disrupts homeostatic, skull bone marrow-derived monocyte and macrophage trajectories in the dura.

immunology↗