Biology subjects

Schutz, C.

Publications and source records attributed to Schutz, C..

3 recordsLinked to original sources

bioRxiv2025

Two distinct cytokine response clusters identified in healthcare workers with apparent resistance to infection with Mycobacterium tuberculosis despite sustained occupational exposure

IntroductionEvidence exists that some individuals resist ("Resisters") Mycobacterium tuberculosis (Mtb) infection despite sustained exposure, but the protective mechanisms involved are not fully understood. We investigated immune responses induced by ex vivo stimulation of peripheral blood mononuclear cells (PBMC) with live Mtb in Resisters compared to those with latent TB infection (LTBI). MethodsHIV-uninfected healthcare workers working in high TB exposure healthcare facilities for over 5 years were screened for Mtb sensitization using the interferon-gamma release assay (IGRA) and the tuberculin skin test (TST). We identified Resisters (TST<10mm and IGRA<0.35 IU/mL, n=129) and those with LTBI (TST[≥]10mm and IGRA[≥]0.35 IU/mL n=145). We selected a subset of extreme resisters (TST=0mm and IGRA<0.2 IU/mL; n=26) and extreme LTBI (TST[≥]15mm and IGRA[≥]1 IU/mL; n=24) for these analyses. Blood was collected and PBMC isolated and cultured with live H37Rv Mtb for 18 hours. Supernatants were collected and used for measuring 65 secreted analytes by Luminex. We also evaluated cell-associated cytokine expression by CD4 T cells and monocytes in these participants using flow cytometry. ResultsUsing the feature selection in R, we identified a set of 4 cytokines: IL-17A, MCP-1, IL-8, and MDC, which collectively classified extreme Resisters from extreme LTBI with an area-under-the-curve (AUC) of 0.67 (0.54-0.85). Focusing only on the extreme Resisters, and using hierarchical clustering, participants in this group segregated into two main clusters (Resister_c1 and Resister_c2). Further analyses identified 37 cytokines that were significantly higher and 15 cytokines that were lower in Resister_c2 compared with Resister_c1. A set of 5 cytokines (TRAIL, MIP-1{beta}, Fractalkine, GRO- and IL-1) collectively classified these two clusters with an AUC of 1 (1-1). CD4 T cell and monocyte responses to Mtb did not significantly differ between the two clusters. ConclusionsMtb-specific immune responses segregate extreme Resisters into two distinct clusters in individuals with apparent resistance to Mtb infection and may allow discrimination of individuals with true resistance from those with infection but have alternative immune responses not detected by IGRA and TST.

immunology↗

bioRxiv2022

Discovery of a new but established population of the guppy in Germany

Feral populations of tropical fish species in temperate climates like Central Europe are a rare but repeatedly observed phenomenon. Due to the influence of industrial or geothermal heated water, released tropical fish may be able to survive harsh winter conditions. Here we characterize a newly discovered thermally polluted river, with an established population of the guppy (Poecilia reticulata) co-occurring with native species. Through a mark-recapture approach, we estimated the population size of the guppies close to the warm water inflow to be around 2000 individuals during summer and we further provide descriptive demographics of this population which allow us to assume it is well established in that river. Further, we found some of the sampled specimen being parasitized by Camallanus roundworms, thus showing the guppies host potential for this genus of internal parasites. The popularity and widespread distribution of guppies as ornamental fish often leads to their intentional or unintentional release into the wild where they are often pioneer species in anthropogenically heavily modified habitats. Guppies threaten native species through niche competition and transmission of diseases. Accordingly, early awareness and knowledge on the status of non-native populations is crucial for effective management strategies.

ecology↗

bioRxiv2019

Closely related Cryptococcus neoformans strains possess differential virulence both in humans and the mouse inhalation model

Cryptococcal meningitis (CM) causes high rates of HIV-related mortality, yet Cryptococcus factors influencing patient outcome are not well understood. Pathogen-specific traits, such as the strain genotype and degree of antigen shedding, are associated with clinical outcome but the underlying biology remains elusive. In this study, we examined factors determining disease outcome in HIV-infected cryptococcal meningitis patients infected with C. neoformans strains with the same multi-locus sequence type. Both patient mortality and survival were observed during infections with the same sequence type. Disease outcome did not correlate with underlying patient immune deficiencies. Patient mortality was associated with higher antigen levels, fungal burden in the CSF, and low CSF fungal clearance. Virulence of a subset of clinical strains with the same sequence type were analyzed using the mouse inhalation model of cryptococcosis. We showed a strong correlation between human and mouse mortality rates, demonstrating the mouse inhalation model recapitulates human infection. Similar to human infection, the ability to multiply in vivo, demonstrated by high fungal burden in the lung and brain tissues, was associated with mouse mortality. Mortality rate was not associated with single C. neoformans virulence factors in vitro or in vivo; rather, a trend in mortality rate correlated with a suite of traits. These observations show that genotype similarities between C. neoformans strains do not necessarily translate into similar virulence either in the mouse model or in human patients. In addition, our results show that in vitro assays do not fully reproduce in vivo conditions that influence C. neoformans virulence.

microbiology↗