Biology subjects

Fricke, S.

Publications and source records attributed to Fricke, S..

6 recordsLinked to original sources

bioRxiv2026

Phagocytosis Events Shift the Activation Trajectory of Neutrophils towards Serial Eating of S. aureus

Neutrophil recruitment and activation are essential for the control of microbial infections, yet how these cells adapt functionally upon entry into inflamed tissues remains incompletely understood. In particular, how temporal cues and direct interaction with the pathogen differentially shape neutrophil heterogeneity and effector functions remains poorly defined. Here, we employed in vivo time-stamping of tissue entry to disentangle time-dependent versus pathogen interaction-specific drivers of neutrophil heterogeneity during S. aureus skin infection. We show that canonical aging and activation markers progressively accumulated with increasing time since arrival in the inflamed tissue. Strikingly, however, phagocytic activity at the single-cell level was uncoupled from tissue dwell time and instead strictly correlated with each neutrophil's history of prior uptake of S. aureus. Furthermore, pathogen engagement induced an immediate shift towards a maximally activated phenotype. Therefore, neutrophil functional heterogeneity in infected tissues is governed less by residence time and more by discrete pathogen encounters which act as a key instructive event for subsequently enhanced phagocytosis. This suggests that the balance of microenvironmental and pathogen-derived cues tailors neutrophil activation in order to optimize antimicrobial clearance.

immunology↗

bioRxiv2026

Mast cells initiate lymphocyte egress from distant lymph nodes upon skin inflammation via a RANKL-sphingosine-1-phosphate axis

Receptor activator of NF{kappa}B ligand (RANKL) is important for bone metabolism, but also modulates immune processes. We showed that mast cells (MCs) are involved in RANKL regulation, but the importance of MC-derived RANKL in skin inflammation has not yet been investigated. In contact hypersensitivity (CHS), the absence of MC-derived RANKL led to reduced skin inflammation due to impaired leukocyte infiltration and blood lymphopenia. Surprisingly, we observed a massive hyperplasia of the distant inguinal lymph nodes in the absence of MC-RANKL. Using adoptive transfers, flow cytometry and whole-mount 3D imaging, we demonstrated that this was not caused by structural maladaptation, but rather by the inability of lymphocytes to exit in a timely manner. Importantly, RANKL deletion in skin MCs only replicated the effect of LN hyperplasia and blood lymphopenia. Moreover, MCs were involved in serum sphingosine-1-phosphate (S1P) regulation during sensitization and challenge. Intravascular administration of S1P restored timely lymphocyte egress, demonstrating a MC-induced organ-spanning RANKL-S1P axis. Consequently, peripheral skin MC-derived RANKL is essential for the timely lymphocyte egress from distant LNs, which may have important implications for the targeted treatment of inflammatory skin diseases.

immunology↗

bioRxiv2026

Anchored for action: a dual role for integrin β1 in mast cell perivascular positioning and vasoactivity to license leukocyte recruitment

Mast cells (MCs) are tissue-resident sentinels of the innate immune system that play pivotal roles in host defense and inflammation. Perivascular MCs exert a particularly strong influence on the onset and dynamics of inflammation through the rapid, directional release of proinflammatory mediators into the circulation. Yet, the mechanisms governing their attachment to the vessel wall - a prerequisite for intravascular degranulation - remain poorly defined. Using a conditional knockout of integrin {beta}1 (Itgb1) in MCs, we investigated how perivascular positioning, degranulation, and vasoactive function contribute to inflammatory responses. In vivo imaging revealed that Itgb1 is essential for positioning MCs within the perivascular niche, particularly around arterioles. The absence of Itgb1 markedly reduced directional MC degranulation into blood vessels during skin inflammation. In vitro, Itgb1-deficient MCs displayed impaired degranulation kinetics together with altered SHIP1/PI3K-AKT signaling and calcium influx upon P2X7 ligation by ATP. During contact hypersensitivity, mice lacking Itgb1 in MCs exhibited strongly diminished ear swelling and reduced recruitment of multiple leukocyte subsets. Mechanistically, disordered MC positioning and attenuated degranulation impaired endothelial activation, resulting in decreased leukocyte adhesion and extravasation. These findings uncover a dual role for Itgb1 in regulating MC responsiveness and pro-inflammatory vasoactive function, establishing Itgb1-mediated perivascular MC positioning as a key prerequisite for effective leukocyte recruitment. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/723399v1_ufig1.gif" ALT="Figure 1"> View larger version (80K): org.highwire.dtl.DTLVardef@2268d8org.highwire.dtl.DTLVardef@1114842org.highwire.dtl.DTLVardef@19efc2borg.highwire.dtl.DTLVardef@bd90cf_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2026

Leishmaniamajor co-opts IL-7 feedback in monocytes to suppress CD4⁺ T-cell immunity

During immune responses, pro-and anti-inflammatory mechanisms must be balanced to ensure pathogen clearance while limiting tissue damage. Monocyte-derived cells contribute to both processes, yet the underlying regulatory circuits remain incompletely defined. Here, we show that a subset of PDPN+IL-7R+ monocyte-derived cells that impair effector CD4 T cell-mediated control of intracellular pathogens, and thus perpetuate the infection. Fibroblast-derived IL-7 drives this immunosuppressive program, which is up-regulated in response to IFN{gamma}. We thus uncover a cytokine-dependent feedback circuit in which elevated IFN{gamma} induces IL-7 production by fibroblasts, licensing immunosuppressive monocyte-derived cells that restrain CD4 T cell responses. This mechanism links excessive inflammation to immune suppression at the expense of pathogen control. Targeting this feedback loop may enable therapeutic strategies that enhance antimicrobial immunity while preserving tissue integrity.

immunology↗

bioRxiv2024

Broad-scale phenotyping in Arabidopsis reveals varied involvement of RNA interference across diverse plant-microbe interactions

RNA interference (RNAi) is a crucial mechanism that can contribute to immunity against infectious microbes through the action of DICER-LIKE (DCL) and ARGONAUTE (AGO) proteins. In the case of the fungal pathogen Botrytis cinerea and the oomycete Hyaloperonospora arabidopsidis, plant DCL and AGO proteins have proven roles as negative regulators of immunity, suggesting functional specialization of these proteins. To address this aspect in a broader taxonomic context, we characterized the colonization pattern of an informative set of DCL and AGO loss-of-function mutants in Arabidopsis thaliana upon infection with a panel of pathogenic microbes with different lifestyles, and a fungal mutualist. Our results revealed that AGO1 and AGO4 function as positive regulators of immunity to a bacterial and a fungal pathogen, respectively. Additionally, AGO2 and AGO10 positively modulated the colonization by a fungal mutualist. Therefore, analysing the role of RNAi across a broader range of plant-microbe interactions has identified previously unknown functions for AGO proteins. For some pathogen interactions, however, all tested mutants exhibited wild type-like infection phenotypes, suggesting that the roles of AGO and DCL proteins in these interactions may be more complex to elucidate.

plant biology↗

bioRxiv2021

A new triple fluorescence reporter system for discrimination of Apobec1 and Apobec3 C-to-U RNA editing activities and editing-dependent protein expression

The human body is composed of many different cell types which communicate with each other. In particular, the brain consists of billions of neurons and non-neuronal cells which are interconnected and require tight and precise regulation of cellular processes. RNA editing is a cellular process that diversifies gene function by enzymatic deamination of cytidine or adenine. This can result in changes of protein structure and function. Altered RNA editing is becoming increasingly associated with all kind of disease, but most approaches use advanced sequencing technologies to analyze bulk material. However, it is also becoming progressively evident that changes in RNA editing have to be analyzed and considered in a cell type specific way. We present here a triple fluorescence reporter system that discriminates between Apobec1- and Apobec3-dependent C-to-U RNA editing at the single cell level. In particular, the Apobec3 reporter enables C-to-U RNA editing inducible protein expression through generation of a RNA splice donor site. We used the new system here to analyze Apobec1- and Apobec3-dependent RNA editing in primary neuron culture. The results reveal a large heterogeneity of C-to-U RNA editing in neurons and glia cells, and they show that GABAergic neurons are not able to perform Apobec1-dependent RNA editing, but Apobec3-dependent editing. Altogether, the new system can be the foundation of therapeutic application systems that counteract changes in Apobec3-dependent RNA editing in disease while simultaneously monitoring Apobec1-dependent RNA editing at the single cell level.

neuroscience↗