Biology subjects

Viemann, D.

Publications and source records attributed to Viemann, D..

4 recordsLinked to original sources

bioRxiv2026

Neonatal liver niches program T cell tolerance

After birth, the immune system must learn to tolerate a rapidly changing milieu of commensals and self while remaining ready for pathogens. Here we characterize the neonatal liver as a central hub in this process: In postnatal week 1-2, the liver hosts a developmentally encoded, microbiota-independent expansion of regulatory T cells (Tregs) that coexists with microbiota-tuned conventional wave of activated CD4 T cells (Tconvs). Mechanistically, the Treg expansion is governed by MHCII-mediated antigen presentation by CCR7+ cDC1s, which establish tolerogenic DC:T cell clusters in the liver parenchyma, allowing for local expansion and control via PD-L1 checkpoints that selectively increase Tregs without unleashing Tconvs. Importantly, this transient, neonatal program predisposes hepatotropic viral infections to progress toward chronic disease but also protects the adult liver from steatotic disease. These data position the neonatal liver as a unique site of early life T-cell education with timing-sensitive implications for early-life interventions.

immunology↗

bioRxiv2025

Global analysis of infant gut microbiota revealed distinctive maturation dynamics across lifestyles

The infant gut microbiome develops during the first years of life and influences long-term health through its interaction with immune system development. However, our understanding of early-life microbiome assembly is biased by the predominance of infants with industrialized lifestyles from North America and Europe. Here, we address this bias by assembling a globally representative dataset of infant gut microbiomes to train a microbiome maturation model that can characterize lifestyle specific patterns of microbial maturation as a function of age. Models trained exclusively on industrialized infants perform poorly when applied to non-industrialized datasets. In contrast, more diverse models including individuals from both lifestyles achieve increased correlation between microbial and chronological age. We identified differences in relevant taxa associated with the maturation in the different lifestyles. Additionally, our modeling approach detects a delay in the microbial maturation of independent cohorts of severely malnourished and preterm infants compared to healthy ones. Our results underscore the relevance of global diversity in microbiome research and provide deeper insights into context-dependent maturation dynamics of the infant gut microbiome.

microbiology↗

bioRxiv2025

Probiotic-conditioned microbiota from preterm infants modulate immune response to pathogen challenge in a humanized mouse model

AbstractEarly-life host-microbe interactions critically shape immune development, lifelong homeostasis, and disease susceptibility. The PRIMAL trial (Priming Immunity at the Beginning of Life) demonstrated that multistrain probiotics shifted the gut microbiota of very preterm infants toward eubiosis without affecting sepsis incidence, yet the immunological consequences remained unresolved. To explore this, we colonized germ-free female mice with fecal samples from probiotic- or placebo-treated preterm infants from the PRIMAL trial. Microbiota composition was vertically transmitted and stable across generations. At steady-state, 3-week-old pups colonized with probiotic-conditioned microbiota exhibited markedly reduced populations of innate immune cells, particularly in the colon, with subtler effects in the small intestine and spleen, while adaptive immune subsets were less affected. Upon enteropathogenic Escherichia coli challenge at day 5, pups harboring probiotic-conditioned microbiota displayed reduced growth and impaired bacterial clearance, correlating with diminished numbers of key innate immune cell populations. These findings demonstrate that probiotic-driven shifts in human-derived microbial communities can attenuate immune cell development in mice and alter early-life infection outcomes. Our study underscores the complex, context-dependent effects of probiotics on the neonatal microbiota-immune axis and provides mechanistic insight into how interventions in preterm infants may influence susceptibility to infection.

immunology↗

bioRxiv2018

Clinical scoring is the most sensitive biomarker detecting developing sepsis in newborn mice

Newborn individuals are highly susceptible to infectious diseases. For better insights into age-specific host-pathogen interactions infection models are increasingly employed in neonatal mice. However, for newborn mice no measures are available to objectify the clinical disease state, particularly not in a longitudinal manner, to meet legal animal welfare requirements. We developed a scoring system for newborn mice that relies on observational and examination-based parameters and validated it by applying a Staphylococcus aureus-induced infection model in two different mouse strains.\n\nThe scoring results strongly correlated with the death kinetics independent of which mouse strain was used. A score above 7 predicted fatality. While the score values increased already at early sepsis stages the large majority of plasma cytokine levels remained comparable to those in uninfected control neonates. The levels of interleukin (Il)-6, chemokine C-C motif ligand 5, Il-1 and tumor necrosis factor were not increased before 24 hours after infection and correlated only at this late stage of sepsis with the scored disease state.\n\nWe propose the first clinical scoring system that serves as important research tool to evaluate the clinical course of sepsis in newborn mice. It detects health impairments of newborn pups in a highly sensitive and longitudinal manner, providing information about the disease severity as well as prognosis.

immunology↗