Biology subjects

Opitz, B.

Publications and source records attributed to Opitz, B..

5 recordsLinked to original sources

bioRxiv2023

IL-33 controls IL-22-dependent antibacterial defense by modulating the microbiota

IL-22 plays a critical role in defending against mucosal infections, but how IL-22 production is regulated is incompletely understood. Here, we show that mice lacking IL-33 or its receptor ST2 (IL-1RL1) were more resistant to Streptococcus pneumoniae lung infection than wild-type animals, and that single nucleotide polymorphisms in IL33 and IL1RL1 were associated with pneumococcal pneumonia in humans. The effect of IL-33 on S. pneumoniae infection was mediated by negative regulation of IL-22 production in innate lymphoid cells (ILCs), but independent of ILC2s as well as IL-4 and IL-13 signaling. Moreover, IL-33s influence on antibacterial defense was dependent on housing conditions of the mice, and mediated by the modulatory effect of IL-33 on the microbiota. Collectively, we provide insight into the bidirectional crosstalk between the innate immune system and the microbiota. We identify a mechanism, dependent on both genetic and environmental factors, that impacts the efficacy of antibacterial immune defense and thus susceptibility to pneumonia. SIGNIFICANCE STATEMENTLower respiratory tract infections are the fifth leading cause of death. Here, we describe a mechanism influenced by genetic and environmental factors that affects the efficacy of pulmonary antibacterial immune responses. We show that IL-33 controls antibacterial defense by regulating the production of IL-22, a cytokine with known functions in antimicrobial immunity in lungs. The effect of IL-33 on IL-22-dependent defense was influenced by the hygienic status of the mice and mediated by IL-33s modulatory effect on the animal microbiota. In addition, genetic variation in genes involved in IL-33 signaling was associated with bacterial pneumonia in humans. Our findings may be important for our understanding of the factors influencing predisposition to lower respiratory tract infections.

immunology↗

bioRxiv2022

Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in severe COVID-19

The clinical course of the 2019 coronavirus disease (COVID-19) is variable and to a substantial degree still unpredictable, especially in persons who have neither been vaccinated nor recovered from previous infection. We hypothesized that disease progression and inflammatory responses were associated with alterations in the microbiome and metabolome. To test this, we integrated metagenome, metabolome, cytokine, and transcriptome profiles of longitudinally collected samples from hospitalized COVID-19 patients at the beginning of the pandemic (before vaccines or variants of concern) and non-infected controls, and leveraged detailed clinical information and post-hoc confounder analysis to identify robust within- and cross-omics associations. Severe COVID-19 was directly associated with a depletion of potentially beneficial intestinal microbes mainly belonging to Clostridiales, whereas oropharyngeal microbiota disturbance appeared to be mainly driven by antibiotic use. COVID-19 severity was also associated with enhanced plasma concentrations of kynurenine, and reduced levels of various other tryptophan metabolites, lysophosphatidylcholines, and secondary bile acids. Decreased abundance of Clostridiales potentially mediated the observed reduction in 5-hydroxytryptophan levels. Moreover, altered plasma levels of various tryptophan metabolites and lower abundances of Clostridiales explained significant increases in the production of IL-6, IFN{gamma} and/or TNF. Collectively, our study identifies correlated microbiome and metabolome alterations as a potential contributor to inflammatory dysregulation in severe COVID-19. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=150 HEIGHT=200 SRC="FIGDIR/small/518860v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@afc4edorg.highwire.dtl.DTLVardef@1a9ac2aorg.highwire.dtl.DTLVardef@65fb46org.highwire.dtl.DTLVardef@153ee6a_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2021

In search for the most optimal EEG method: A practical evaluation of a water-based electrode EEG system.

The study assessed a mobile electroencephalography (EEG) system with water-based electrodes for its applicability in cognitive and behavioural neuroscience. It was compared to a standard gel-based wired system. EEG was recorded on two occasions (first with gel-based, then water-based system) as participants completed the flanker task. Technical and practical considerations for the application of the water-based system are reported based on participant and experimenter experiences. Empirical comparisons focused on EEG data noise levels, frequency power across four bands (theta, alpha, low beta and high beta) and event-related components (P300 and ERN). The water-based system registered more noise compared to the gel-based system which resulted in increased loss of data during artefact rejection. Signal to noise ratio was significantly lower for the water-based system in the parietal channels which impacted the observed parietal beta power. It also led to a shift in topography of the maximal P300 activity from parietal to frontal regions. It is also evident, that the water-based system may be prone to slow drift noise which may affect the reliability and consistency of low frequency band analyses. Practical considerations for the use of water-based electrode EEG systems are provided.

neuroscience↗

bioRxiv2020

Error-related cognitive control and behavioural adaptation mechanisms in the context of motor functioning and anxiety.

Previous research suggests that there is an interaction between cognitive and motor processes. This has been investigated throughout development and in different conditions related to motor impairment. The current study addressed a gap in the literature by investigating this interaction in the general population of healthy adults with different profiles of motor proficiency by focusing on error-related cognitive control and behavioural adaptation mechanisms. In addition, the impact of these processes was assessed in terms of experienced anxiety. Forty healthy adults were divided into high and low motor proficiency groups based on an assessment of their motor skills. Using electroencephalography (EEG) during a flanker task, error-related negativity (ERN) was measured as the neural indicator of cognitive control. Post-error slowing (PES) was measured to represent behavioural adaptation. Participants also completed an anxiety assessment questionnaire. Participants in the high motor proficiency group achieved better task accuracy and showed relatively enhanced cognitive control through increased ERN. Contrastingly, individuals in the lower motor proficiency group achieved poorer accuracy whilst showing some evidence of compensation through increased PES. Anxiety was found to be associated with motor functioning, but the study could not provide evidence that this was related to cognitive or behavioural control mechanisms. The interaction between cognitive and motor processes observed in this study is unique for healthy and sub-clinical populations and provides a baseline for the interpretation of similar investigations in individuals with motor disorders.

neuroscience↗

bioRxiv2020

Motor and non-motor sequence prediction is equally affected in children with Developmental Coordination Disorder

Children with Developmental Coordination Disorder (DCD) are diagnosed based on motor difficulties. However, they also exhibit difficulties in several other cognitive domains, including visuospatial processing, executive functioning and attention. One account of the difficulties seen in DCD proposes an impairment in internal forward modelling, i.e., the ability to (i) detect regularities of a repetitive perceptual or motor pattern, (ii) predict future outcomes of motor actions, and (iii) adapt behaviour accordingly. Using electroencephalographic recordings, the present study aimed to delineate these different aspects of internal forward modelling across several domains. To this end, 24 children with DCD and 23 typically-developing children (aged 7-10 years) completed a serial prediction task in the visual, temporal, spatial and motor domains. This task required them to learn short sequences and to indicate whether a sequence was disrupted towards its end. Analyses revealed that, across all domains, children with DCD showed poorer discrimination between intact and disrupted sequences, accompanied by a delayed late parietal positivity elicited by disrupted sequences. These results indicate an impairment in explicit sequence discrimination in DCD across motor and cognitive domains. However, there is no evidence for an impairment in implicit performance on the motor task in DCD. These results suggest an impairment of the updating of an internal forward model in DCD resulting in a blurred representation of that model and consequently in a reduced ability to detect regularities in the environment (e.g., sequences). Such a detailed understanding of internal forward modelling in DCD could help to explain the wide range of co-occurring difficulties experienced by those with a diagnosis of DCD.

neuroscience↗