Biology subjects

Knolle, P.

Publications and source records attributed to Knolle, P..

5 recordsLinked to original sources

bioRxiv2026

Long-term Humoral Immune Dynamics After SARS-CoV-2 Vaccination and Infection in Healthcare Workers: The VaCoMRI Study

ObjectivesThe VaCoMRI study tracked a healthcare worker cohort from 2020 through June 2024 to characterize the long-term sustainability of vaccine- and infection-induced SARS-CoV-2 immunity. MethodsFollowing an initial anti-nucleocapsid (N) IgG screening of 4,554 employees in early 2020, participants were monitored regularly from the BNT162b2 rollout (December 2020). Serum collected at predefined intervals after vaccination and breakthrough infection (BTI) was analyzed for anti-N, quantitative anti-spike (anti-S) IgG, and surrogate viral neutralizing antibody (sVNT) titers. ResultsOver a median follow-up of 1,180 days, 142 healthcare workers contributed longitudinal samples; 66.2% experienced one BTI and 14.1% a second. In previously seronegative individuals, anti-N titers decreased 2.3-fold between 3 and 6 months post-first BTI, with seropositivity dropping from 82% to 40.4% (median time to seronegativity: 179 days). Conversely, prior anti-N seropositivity was associated with 4.5-fold higher anti-N IgG levels during follow-up, and a second BTI led to 3-fold higher titers at 3 months. Before BTI, the third vaccine dose significantly enhanced antibody persistence versus the second dose; at 9 months, titers remained 7.2-fold higher for sVNT and 3.9-fold higher for anti-S IgG. Initial seropositivity also predicted 2.9-fold higher sVNT levels during follow-up. ConclusionsRepeated vaccination and infection synergistically induced robust, durable spike-directed hybrid immunity. Conversely, rapid anti-N IgG waning severely limits its reliability for the retrospective serosurveillance of SARS-CoV-2 exposure in occupational settings.

microbiology↗

bioRxiv2025

Single cell decomposition of multicellular aging programs associated with impaired lung regeneration

Aging impairs the regenerative capacity of mammalian organs and is a major risk factor for organ fibrosis. Mechanisms underlying persistent fibrosis after lung injury in old individuals remain unclear. We used longitudinal single-cell RNA-seq after lung injury and dissected aging effects computationally and experimentally at baseline and during repair. In old mice, sustained fibroblast activation in the resolution phase of fibrosis was associated with prolonged epithelial senescence and persistent epithelial-mesenchymal crosstalk. Single-cell interpretable tensor decomposition analysis revealed that aging most strongly affected T/B-lymphocytes and macrophages. Notably, we identified a Granzyme K-high CD8+ T cell state that was unique to aged mice, co-localized with epithelial progenitors, and its co-culture or Gzmk treatments in lung organoids impaired progenitor function by inducing stem cell senescence. In summary, our study highlights the effects of immune aging on epithelial progenitor function and provides a time-resolved high resolution map of lung regeneration in the context of aging.

cell biology↗

bioRxiv2022

The lncRNA landscape of cardiac resident macrophages and identification of Schlafenlnc as a regulator of macrophage migratory function

Cardiac resident macrophages (crMPs) were recently shown to exert pivotal functions in cardiac homeostasis and disease, but the underlying molecular mechanisms are largely unclear. Long non-coding RNAs (lncRNAs) are increasingly recognized as important regulatory molecules in a number of cell types, but neither the identity nor the molecular mechanisms of lncRNAs in crMPs are known. Here, we have employed deep RNA-seq and single cell RNA sequencing to resolve the crMP lncRNA landscape from healthy and diseased murine myocardium. CrMPs express previously unknown and highly cell type-specific lncRNAs, among which one lncRNA, termed Schlafenlnc, was particularly abundant and enriched in crMPs. We found Schlafenlnc to be necessary for migration-associated gene expression in macrophages in vitro and in vivo and essential for their adhesion and migration. Collectively, our data provide a basis to the systematic characterization of lncRNAs in crMPs and establish Schlafenlnc as a critical regulator of macrophage migratory functions.

cell biology↗

bioRxiv2022

Suppression of systemic T cell immunity to viral infection during liver injury is prevented by inhibition of interferon and IL-10 signaling

Patients with liver injury such as cirrhosis are at increased risk of intractable viral infections and are hyporesponsive to vaccination. Here, we report that liver injury leads to inhibition of systemic T cell immunity (LIST), which abrogated anti-viral immunity and caused persistent infection in preclinical liver injury models. Enhanced gut microbial-translocation but not dysbiosis induced tonic type-I-interferon (IFN) signaling in hepatic myeloid cells, which was responsible for their excessive production of IL-10 after viral infection. Antibiotic treatment reducing intestinal microbial burden or inhibition of IFN- and IL-10-signaling all restored anti-viral immunity without immune pathology. Importantly, inhibition of IL-10 restored virus-specific immune responses to vaccination in cirrhotic patients. Thus, LIST results from sequential events involving intestinal microbial translocation, hepatic myeloid cell-derived IFN-/IL-10 expression, and finally inhibitory IL-10 receptor-signaling in T cells, of which IL-10R-signaling may serve as target to reconstitute anti-viral T cell immunity in cirrhotic patients.

immunology↗

bioRxiv2018

Sodium chloride is an ionic checkpoint for human Th2 cell responses and shapes the atopic skin microenvironment

One sentence summarySodium is an ionic checkpoint for the induction and amplification of human Th2 cell responses and shapes the atopic skin microenvironment, where it could serve as a novel therapeutic target for Th2 mediated diseases.\n\nAbstractThere has been a strong increase in the incidence of allergic diseases over the last 50 years. Environmental factors most likely account for this phenomenon. However, the nature of these factors and the mode of action by which they induce the type 2 immune deviation, which is characteristic of atopic diseases, remains unclear. It has previously been reported that dietary sodium chloride promotes the polarization of Th17 cells with implications for autoimmune diseases such as multiple sclerosis. Here, we demonstrate that sodium chloride also potently promotes Th2 cell responses on multiple regulatory levels. Sodium chloride enhanced IL-4 and IL-13 production while suppressing IFN-{gamma} production in effector T cells. It diverted alternative T cell fates into the Th2 cell phenotype and also induced de novo Th2 cell polarization from naive T cell precursors. Mechanistically, it exerted its effects via the osmosensitive transcription factor NFAT-5 and the kinase SGK-1, which regulated Th2 signature cytokines and master transcription factors in hyperosmolar salt conditions. The skin of patients suffering from atopic dermatitis contained highly elevated amounts of sodium compared to non-lesional atopic and healthy skin. This demonstrates that sodium chloride represents a so far overlooked cutaneous microenvironmental factor in atopic dermatitis that can induce Th2 cell responses, the orchestrators of allergic diseases. Together, our data propose ionic signaling through sodium chloride as a novel checkpoint and potential therapeutic target for type 2 immunity and its associated allergic diseases.

immunology↗