Biology subjects

Krone, M.

Publications and source records attributed to Krone, M..

3 recordsLinked to original sources

bioRxiv2023

M. tuberculosis antigen-responsive IL17+ CD4 T cells are disproportionately spared in ART-suppressed HIV

BackgroundInterleukin 17 producing CD4 T cells contribute to the control of Mycobacterium tuberculosis (Mtb) infection in humans; whether infection with Human Immunodeficiency Virus (HIV) disproportionately affects distinct Th17 cell subsets that respond to Mtb is incompletely defined. MethodsWe performed high-definition characterization of circulating Mtb-specific Th17 cells by spectral flow cytometry in people with latent TB and treated HIV (HIV-ART). We also measured kynurenine pathway activity by LC/MS on plasma and tested the hypothesis that tryptophan catabolism influences Th17 cell frequencies in this context. ResultsWe identified two subsets of Th17 cells: subset 1 defined as CD4+V7.2-CD161+CD26+ and subset 2 defined as CD4+V7.2-CCR6+CXCR3- cells of which subset 1 was significantly reduced in LTBI with HIV-ART, yet Mtb-responsive IL17-producing CD4 T cells were preserved; we found that IL17-producing CD4 T cells dominate the response to Mtb antigen but not CMV antigen or staphylococcal enterotoxin B (SEB); and tryptophan catabolism negatively correlates with both subset 1 and subset 2 Th17 cell frequencies. ConclusionsWe found differential effects of ART-suppressed HIV on distinct subsets of Th17 cells, that IL17-producing CD4 T cells dominate responses to Mtb but not CMV antigen or SEB, and that kynurenine pathway activity is associated with decreases of circulating Th17 cells that may contribute to tuberculosis immunity.

immunology↗

bioRxiv2021

OmicsTIDE: Interactive Exploration of Trends in Multi-Omics Data

MotivationThe increasing amount of data produced by omics technologies has significantly improved the understanding of how biological information is transferred across different omics layers and to which extent it is involved in the manifestation of a given phenotype. Besides data-driven analysis strategies, interactive visualization tools have been developed to make the analysis in the multi-omics field more transparent. However, most state-of-the-art tools do not reconstruct the impact of a given omics layer on the final integration result. In general, the amount of omics data analyses strategies and the fields of applications lack a clearer classification of the different approaches. ResultsWe developed a classification for omics data focusing on different aspects of multi-omics data sets, such as data type and experimental design. Based on this classification we developed the Omics Trend-comparing Interactive Data Explorer (OmicsTIDE), an interactive visualization tool developed to address the limitations of current visualization approaches in the multi-omics field. The tool consists of an automated part that clusters omics data to determine trends and an interactive visualization. The trends are visualized as profile plots and are connected by a Sankey diagram that allows an interactive pairwise trend comparison to discover concordant and discordant trends. Moreover, large-scale omics data sets are broken down into small subsets of concordant and discordant regulatory trends within few analysis steps. We demonstrate the interactive analysis using OmicsTIDE with two case studies focusing on different types of experimental designs. AvailabilityOmicsTIDE is a web tool and available via http://tuevis.informatik.uni-tuebingen.de/ Contactkay.nieselt@uni-tuebingen.de

bioinformatics↗

bioRxiv2020

TCF-1 regulates the stem-like memory potential of HIV-specific CD8+ T cells in elite controllers

Although many HIV cure strategies seek to expand HIV-specific CD8+ T cells to control the virus, all are likely to fail if cellular exhaustion is not prevented. A loss in stem-like memory properties (i.e., the ability to proliferate and generate secondary effector cells) is a key feature of exhaustion; little is known, however, about how these properties are regulated in human virus-specific CD8+ T cells. We found that virus-specific CD8+ T cells from humans and non-human primates naturally controlling HIV/SIV infection express more of the transcription factor, TCF-1, than non-controllers. HIV-specific CD8+ T cell TCF-1 expression correlated with memory marker expression and proliferative capacity and declined with antigenic stimulation. CRISPR-Cas9 editing of TCF-1 in human primary T cells demonstrated a direct role in regulating expansion capacity. Collectively, these data suggest that TCF-1 controls the stem-like memory properties of HIV-specific CD8+ T cells and provides a rationale for enhancing this pathway in T cell-based therapeutic strategies for HIV. One Sentence SummaryTCF-1 is highly expressed in HIV-specific CD8+ T cells from elite controllers and directly regulates human CD8+ T cell expansion capacity in response to T cell receptor stimulation.

immunology↗