Dataset Information

Significant Differences in Host-Pathogen Interactions Between Murine and Human Whole Blood.

ABSTRACT: Murine infection models are widely used to study systemic candidiasis caused by C. albicans. Whole-blood models can help to elucidate host-pathogens interactions and have been used for several Candida species in human blood. We adapted the human whole-blood model to murine blood. Unlike human blood, murine blood was unable to reduce fungal burden and more substantial filamentation of C. albicans was observed. This coincided with less fungal association with leukocytes, especially neutrophils. The lower neutrophil number in murine blood only partially explains insufficient infection and filamentation control, as spiking with murine neutrophils had only limited effects on fungal killing. Furthermore, increased fungal survival is not mediated by enhanced filamentation, as a filament-deficient mutant was likewise not eliminated. We also observed host-dependent differences for interaction of platelets with C. albicans, showing enhanced platelet aggregation, adhesion and activation in murine blood. For human blood, opsonization was shown to decrease platelet interaction suggesting that complement factors interfere with fungus-to-platelet binding. Our results reveal substantial differences between murine and human whole-blood models infected with C. albicans and thereby demonstrate limitations in the translatability of this ex vivo model between hosts.

SUBMITTER: Machata S

PROVIDER: S-EPMC7843371 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Significant Differences in Host-Pathogen Interactions Between Murine and Human Whole Blood.

Machata Silke S Sreekantapuram Sravya S Hünniger Kerstin K Kurzai Oliver O Dunker Christine C Schubert Katja K Krüger Wibke W Schulze-Richter Bianca B Speth Cornelia C Rambach Günter G Jacobsen Ilse D ID

Frontiers in immunology 20210115

Murine infection models are widely used to study systemic candidiasis caused by C. albicans. Whole-blood models can help to elucidate host-pathogens interactions and have been used for several Candida species in human blood. We adapted the human whole-blood model to murine blood. Unlike human blood, murine blood was unable to reduce fungal burden and more substantial filamentation of C. albicans was observed. This coincided with less fungal association with leukocytes, espec ...[more]

PMID: 33519798

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Project description:The goal of this project is to understand the etiology and pathology of host-pathogen interaction using high-throughput cellular phenotyping. By combining the expertise in pathogen biology, informatics and stem cell biology across the institute, this project will use targeted genetic modification in mouse embryonic stem cells to identify functions of host genes in innate immunity. We will also explore the biology of mouse embryonic stem cells and their differentiation into immune competent cells. To this end we will generate homozygous and inducible knockout lines in mouse embryonic stem cells, which will be differentiated into immune competent cells, such as macrophages or dendritic cells. These will be subjected to a panel of immune challenge and stimulation assays to characterise the functions of the disrupted genes. To identify new functions for mammalian genes in innate immunity we will:\Generate a panel of homozygous inducible gene knockout mouse ES cell lines working from a list of ca. 80 candidate genes (MGP phenotyping and GWAS hits). \Scale up differentiation protocols for immune challenge and stimulation assays.\Benchmark in vitro differentiated ES cell models against primary immune cells from selected MGP mouse lines and eventually against human iPS cells.\Screen a panel of 30 genetically modified cell lines in immunological challenge and stimulation assays, defining phenotypes at the cellular level by high content imaging, biochemically by assaying cytokine production, and at the molecular level by transcriptome analysis.\Define novel gene functions in innate immunity through network analysis of gene expression data from all challenged cell lines.\In the longer term scale up the production and phenotyping of genetically modified cell lines (mouse or human as appropriate).This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

Dataset Information

Significant Differences in Host-Pathogen Interactions Between Murine and Human Whole Blood.

Publications

Significant Differences in Host-Pathogen Interactions Between Murine and Human Whole Blood.

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