Biology subjects

Baasch, S.

Publications and source records attributed to Baasch, S..

6 recordsLinked to original sources

bioRxiv2026

M-CSF drives alveolar macrophage plasticity during development and cytomegalovirus infection

Alveolar macrophages (AM), the most frequent resident immune cells of the lung, are at the first line of defence against respiratory pathogens and instruct structural lung cells, e.g. in tissue repair. They are long-lived and receive their terminal phenotypic imprint through signals originating from the unique location at the tissue-air interface, as well as through cytokines like granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-{beta} (TGF-{beta}). However, the regulatory mechanisms governing their phenotypic plasticity, which is conceptually critical for their positioning and differentiation in early life and for their functional adaptation during infection, remain poorly defined. Here we explored respiratory tract infection with cytomegalovirus (CMV), which is closely linked to mammalian immune evolution. Complementary host-pathogen fate-mapping strategies revealed AM to constitute the bottleneck for efficient mouse (M)CMV infection. MCMV infection induced macrophage colony-stimulating factor (M-CSF) in the alveolar space, and culturing of AM in M-CSF led to a profound remodelling of morphology, immunophenotype, and transcriptional identity, e.g. it increased the expression of interferon-stimulated genes (ISG), which modulated susceptibility to infection. Notably, already at baseline recently differentiated neonatal AM across species retained an M-CSF-associated transcriptional program. This was linked to reduced permissiveness to respiratory MCMV infection in vivo. Overall, our findings identify the role of M-CSF-dependent signalling in conferring plasticity to AM, when it is most needed, particularly during early-life establishment and in response to viral infection.

immunology↗

bioRxiv2026

Preimplantation factor (PIF) is an endogenous inhibitor of potassium channel KV1.3 regulating neutrophil function during pregnancy

Pregnancy is a unique period regarding immune cell regulation. Within the placenta, maternal immune cells play a central role in immune surveillance and tissue remodeling. However, regulatory mechanisms of systemic immunity during pregnancy are less clear. Here, we show that neutrophil function is altered in pregnant mice (E13.5), indicated by increased slow rolling velocity and reduced adhesion. Mechanistically, PreImplantation factor (PIF), a 15 amino acid peptide which is produced by human and murine trophoblast cells of the placenta, is continuously secreted into the maternal circulation and plays a key role in modulating neutrophil function via blocking the voltage-gated potassium channel KV1.3. This resulted in impaired intracellular Ca2+ signaling and subsequently disturbance of neutrophil post-arrest modifications and a higher susceptibility to physiological shear forces in vivo and in vitro. Furthermore, PIF-mediated KV1.3 blockade impaired E-selectin-mediated release of S100A8/A9 and phagocytosis. Taken together, we have identified PIF as an important modulator of neutrophil function during pregnancy suggesting a critical role in regulating innate immune responses throughout gestation.

immunology↗

bioRxiv2026

Macrophage renewal in the small intestine governs early-life control of streptococci

Group B Streptococcus (GBS) is both a common intestinal colonizer that is transmitted intergenerationally, and a primary cause of neonatal sepsis worldwide. However, the innate immune mechanisms that restrict the pathogen at the intestinal barrier early in life remain poorly understood. Using an enteral GBS-colonization model in infant mice, we found that lamina-propria (LP) macrophages controlled both GBS-colonization densities and invasion in an age-dependent fashion. LP macrophages turnover and differentiation were strongly impacted by topology. In the small intestine, monocytes infiltration of the LP occurred from birth on in response to perinatally acquired microbiota, whereas in the colon it was driven by the weaning reaction. Moreover, macrophages of the small intestine mounted a robust, MyD88-dependent inflammatory response to GBS, while those of the colon remained largely unaffected. Together, these findings demonstrate that region-specific macrophage dynamics early in life critically influence host-pathogen-interactions during GBS-colonization.

immunology↗

bioRxiv2026

Crosstalk between Stromal cells and Macrophages Shapes Host Immunity to Mycobacteria

Granulomas are disease-defining heterocellular tissue structures in mycobacterial infections. They play a multifaceted role ranging from containing the pathogen to causing tissue destruction. Here, we established a mature peritoneal granuloma model in C57BL/6 mice to investigate the dynamic cell-cell interactions during mycobacterial infection, including long-term immune alterations in serous cavities as important sites of disease manifestation. We found that mycobacteria reside in stromal cells, which actively modulate the local tissue environment and shape macrophage responses, particularly through formation of chemokines and colony-stimulating factor 1. Chronic infection induces sustained reprogramming and diversification of stromal cells toward specialized, immune-like states, including active transfer of mycobacteria to macrophages and a pronounced interferon response. Consequently, stromal cells acquire immunoregulatory properties and support pathogen handling, monocyte recruitment and macrophage maturation, thereby playing a decisive role in granuloma formation and thus in the immune response to mycobacteria. HIGHLIGHTSO_LIA novel peritoneal mycobacterial infection model reveals heterocellular crosstalk in mature granulomas. C_LIO_LIMycobacterial infections persistently reshape immune architecture of serous cavities as important disease sites. C_LIO_LIStromal cells act as mycobacterial host cells and acquire immune effector functions. C_LIO_LIStromal cells co-organize the tissue host-pathogen interface by recruiting and directly communicating with bone marrow-derived monocytes. C_LI

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↗