Biology subjects

Wackerbarth, L. M.

Publications and source records attributed to Wackerbarth, L. M..

4 recordsLinked to original sources

bioRxiv2026

Development of circadian immune regulation in early life

Circadian rhythms temporally regulate immune cell trafficking, abundance, and immune responsiveness in adults, yet how this rhythmic organization emerges during postnatal development remains unknown. Here, we systematically investigated the establishment and development of circadian immune regulation across multiple biological levels. Leukocyte rhythmicity was not present at birth but was gradually established and strengthened during postnatal development in a leukocyte subset-dependent manner. In parallel, promigratory markers displayed dynamic and heterogeneous developmental trajectories, indicating progressive coordination of rhythmic promigratory programs. At the systemic level, peripheral clocks matured and synchronized during development, with tissue- and clock-gene-dependent differences in the acquisition timing, peak phase, and amplitude of circadian oscillations. This multi-level analysis identifies postnatal development as a dynamic period during which circadian immunity is progressively consolidated through leukocyte rhythmicity, regulation of promigratory factors, and peripheral clocks.

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

Neutrophils are critical for placental and fetal infection with the human pathogen Listeria monocytogenes

Fetal listeriosis, caused by Listeria monocytogenes (Lm), represents a severe infectious disease. During pregnancy, the unique intrauterine environment permits Lm to breach the maternal-fetal barrier by infiltrating the placental trophoblast layer and ultimately leading to significant fetal morbidity and mortality. However, the exact pathways remain incompletely understood. In this study, we sought to elucidate the molecular mechanisms underlying the early stages of placental and fetal Lm infection. Our results reveal that neutrophils serve as a survival niche for Lm within the vasculature, facilitating placental and fetal infection in the mouse in vivo. This finding was further substantiated by in vitro studies using TLR2-stimulated trophoblast cells and Lm-infected neutrophils. Additionally, tissue-clearing analysis of Lm-infected placentas demonstrated neutrophil colocalization with Lm is rare within placental tissue. Collectively, our findings identify maternal neutrophils as an essential viability niche for Lm enabling their entry into trophoblast cells, thereby promoting placental and fetal infection. One Sentence SummaryMaternal circulating neutrophils act as survival niche for Listeria monocytogenes and facilitate placental/fetal infection with Listeria during pregnancy.

immunology↗

bioRxiv2021

Microthrombocytopenia caused by impaired microtubule stability in RhoB-deficient mice

Megakaryocytes are large cells in the bone marrow, which give rise to blood platelets. Platelet biogenesis involves megakaryocyte maturation, the localization of mature cells in close proximity to bone marrow sinusoids and the formation of protrusions, which are shed into the circulation. Rho GTPases play important roles in platelet biogenesis and function. RhoA-deficient mice display macrothrombocytopenia and a striking mislocalization of megakaryocytes into bone marrow sinusoids and a specific defect in G-protein signaling in platelets. However, the role of the closely related protein RhoB in megakaryocytes or platelets remains unknown. In this study, we show that, in contrast to RhoA deficiency, genetic ablation of RhoB in mice results in microthrombocytopenia (decreased platelet count and size). RhoB-deficient platelets displayed mild functional defects predominantly upon induction of the collagen/glycoprotein VI pathway. Megakaryocyte maturation and localization within the bone marrow, as well as actin dynamics were not affected in the absence of RhoB. However, in vitro generated proplatelets revealed pronouncedly impaired microtubule organization. Furthermore, RhoB-deficient platelets and megakaryocytes displayed selective defects in microtubule dynamics/stability, correlating with pronouncedly reduced levels of acetylated -tubulin. Our findings imply that absence of this tubulin posttranslational modification results in decreased microtubule stability leading to microthrombocytopenia in RhoB-deficient mice. Our data thus points to specifically impaired microtubule - but not actin - dynamics as a general mechanism underlying the manifestation of microthrombocytopenia in vivo. We furthermore demonstrate that RhoA and RhoB have specific, non-redundant functions in the megakaryocyte lineage. KEY POINTSO_LIRhoB-deficient mice display microthrombocytopenia C_LIO_LIRhoB has different functions in the megakaryocyte lineage than RhoA and regulates microtubule dynamics C_LI

cell biology↗