Biology subjects

Roesner, L. M.

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

3 recordsLinked to original sources

bioRxiv2024

Different CMV-specific effector T cell subtypes are associated with age, CMV serostatus, and increased systolic blood pressure

Cytomegalovirus (CMV) infection is one of the most common infections in humans, and CMV antigens are the major drivers of repetitive T-cell stimulation as a part of a well-adapted immune response in immunocompetent individuals. With higher age, the recurrent clonal expansion of CMV-specific T cells results in high frequencies of CMV-specific effector T cells. CMV seropositivity has also been linked to arterial stiffness and an increased risk of developing cardiovascular diseases (CVD). The RESIST Senior Individuals (SI) cohort is a population-based cohort with focus on the elderly, established to shed light on the age-related changes of the immune system and the accompanied reduced capability to fight infectious diseases. Here we investigated the frequency and phenotype of CMVpp65-specific CD8+ T cells in the circulation of individuals of different age groups by means of MHC-I tetramer staining and their associations with age and associated factors such as serostatus and blood pressure. In the SI cohort, the frequency of CMV-specific T cells within the CD8+ T cell fraction was increased with age, as previously reported. We add to previous knowledge by showing that this frequency is associated with the total percentage and absolute counts of CD8+ and CD4+CD8+ double-positive T cells within leukocytes. Systolic blood pressure (SBP) and history of CVD correlated with the frequency of CMV-specific CD8+ T cells. Focusing on CMV-specific T cell subtypes, we show here that the frequencies of TEM and CD27-expressing TEMRA cells were associated with higher age. TEM and CD27- TEMRA cell frequencies were increased in donors with high CMV-IgG titers. Furthermore, SBP significantly correlated with CMV-specific effector CD8+ T cells, which was mostly reflected by CD27- TEMRA cells. In conclusion, different effector T-cell subtypes were associated with age, serostatus and SBP, suggesting that it is not age per se that renders elderly CMV-positive individuals susceptible to CVD, but the immune response to CMV. Our study suggests that detailed immunophenotyping may identify individuals whose immune systems are strongly influenced by the response to CMV, leading to health consequences and impairing healthy aging.

immunology↗

bioRxiv2024

The deubiquitinating enzyme CYLD impairs NF-κB- and STAT1-dependent macrophage intrinsic immunity to Staphylococcus aureus

In atopic dermatitis (AD), lesional skin is frequently colonized by Staphylococcus (S.) aureus, contributing to the severity and clinical symptoms of the disease. The inflammatory milieu in the skin is characterized by a type 2 inflammatory signature, including M2 macrophages, which cannot eradicate S. aureus. Since S. aureus is effectively controlled in macrophages activated by pattern recognition receptor (PRR)-induced NF-{kappa}B and interferon (IFN)-{gamma}-induced STAT1 stimulation, we hypothesized that pre-treatment with LPS as a PRR/TLR4-activating agent and IFN-{gamma} would induce effective control of S. aureus in monocyte-derived macrophages (MDMs) of AD patients. Our data show that the deubiquitinating enzyme CYLD is strongly expressed in skin macrophages and MDMs from AD patients compared to healthy controls and impairs the anti-staphylococcal activity of PRR-activated and IFN-treated MDMs. Functionally, CYLD impaired M1 macrophage polarization, as evidenced by reduced expression of CD80, TNF, and IL-6 upon LPS- and IFN-{gamma} treatment in CYLD-deficient as compared to wild-type (WT) MDM/THP1 macrophages. Mechanistically, CYLD inhibited IFN-{gamma}-induced STAT1 phosphorylation and activation by binding to STAT1 and inducing its K63 deubiquitination. CYLD also interacted with TRAF6 and NEMO/IKK{gamma} in the MYD88 signaling pathway and with RIPK2 in the NOD2 pathway, leading to impaired activation of NF-{kappa}B. Inhibition of both STAT1 by siRNA and NF-{kappa}B by IKK inhibitor treatment, respectively, independently abolished the control of S. aureus in both CYLD-deficient and WT THP1 macrophages, which harbored identical high numbers of the pathogen. The in vivo inhibitory function of CYLD on the control of S. aureus was also observed upon infection of Cyld-deficient and WT mice. Collectively, these data illustrate that the increased expression of CYLD in macrophages of AD patients is a factor contributing to the ineffective control of S. aureus, diminishes M1 macrophage polarization, and that CYLD deletion unleashes the break on effective STAT1 and NF-{kappa}B-dependent control of S. aureus.

immunology↗

bioRxiv2024

Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traits

Elderly individuals have higher disease susceptibility and lower vaccine responsiveness, highlighting the need to better comprehend the aging immune system and its clinical associations. Here we conducted a deep immune profiling study of 550 elderly individuals (61-94 years) and 100 young adults (22-38 years). Utilizing high-dimensional spectral flow cytometry to identify 97 immune cell populations and 48-plex cytokine profiling, we detailed intricate age-and sex-related changes in the elderly immune system at an unprecedented depth. Synthesizing information from clinical, laboratory, and immunological data through an integrative multi-block analysis, we reveal overarching systems-level signatures of aging, such as increased concentrations of specific cytokines and frequencies of defined innate and adaptive immune cell subpopulations. Extending this approach, we identified unique immune signatures of smoking, obesity, and several diseases including osteoporosis, heart failure and gout. Our systems biology approach enables to uncover new relationships between clinical characteristics and immunological traits.

immunology↗