No abstract

This version is available at https://strathprints.strath.ac.uk/60486/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Establishing a definitive diagnosis of pneumonia using conventional tests is difficult and expensive. Lateral flow immunoassays (LFIAs) are an advantageous point of care (POC) test option, but they have some limitations in terms of detection and quantification. In this work we have developed a lateral flow immunoassay for the ultrasensitive detection of penumolysin employing plasmonic Surface-Enhanced Resonance Raman Scattering (SERRS) tag as labelled probe. The combination of Au@Ag core-shell nanoparticles as plasmonic platform and Rhodamine B Isothiocyanate as Raman reporter has allowed us to fabricate a SERRS tag with high efficiency and reliability. The limit of quantification of the SERRS-based LFIA was 1 pg/mL, while the limit of detection was 3.6 pg/mL. This could be a strong foundation for a pneumonia diagnosis test based on pneumolysin detection..

Previous work has demonstrated that Trypanosoma brucei occupy several adipose tissue depots, including the subcutaneous adipose tissue in mice and humans, and due to its proximity to the skin, it is proposed to be an important for transmission. Here, we demonstrate that parasites in the inguinal white adipose tissue (iWAT) niche induce sexually dimorphic responses. During infection, male mice experience reduced adipose tissue mass, altered tissue function, and changes in feeding behaviour, whereas females do not. This tissue impairment correlates with an accumulation of TH17 T cells in the iWAT. Genetic ablation of IL-17A/F abolishes infection-associated weight loss and alters feeding behaviour, limiting tissue wasting in male mice. Importantly, we detected a significant elevation in serum IL-17A in sleeping sickness patients, indicating that IL-17A/F signalling is also conserved in humans. We propose a model whereby IL-17A/F acts locally in adipocytes via engagement with its cognate receptor leading to lipolysis and tissue wasting, and/or systemically, via signalling in the hypothalamus to modulate feeding behaviour. Together, our findings suggest key sex-dependent roles for IL-17A/F in regulating adipose tissue and energy balance, as well as a coordinator of brain-adipose tissue communication during sleeping sickness, opening new directions to understand energy balance during infection.

Human African Trypanosomiasis (HAT) has been responsible for several deadly epidemics throughout the 20th century, but a renewed commitment to disease control has significantly reduced new cases and motivated a target for the elimination of Trypanosoma brucei gambiense-HAT by 2030. However, the recent identification of latent human infections, and the detection of trypanosomes in extravascular tissues hidden from current diagnostic tools, such as the skin, has added new complexity to identifying infected individuals. New and improved diagnostic tests to detect Trypanosoma brucei infection by interrogating the skin are therefore needed. Recent advances have improved the cost, sensitivity and portability of Raman spectroscopy technology for non-invasive medical diagnostics, making it an attractive tool for gambiense-HAT detection. The aim of this work was to assess and develop a new non-invasive diagnostic method for T. brucei through Raman spectroscopy of the skin. Infections were performed in an established murine disease model using the animal-infective Trypanosoma brucei brucei subspecies. The skin of infected and matched control mice was scrutinized ex vivo using a confocal Raman microscope with 532 nm excitation and in situ at 785 nm excitation with a portable field-compatible instrument. Spectral evaluation and Principal Component Analysis confirmed discrimination of T. brucei-infected from uninfected tissue, and a characterisation of biochemical changes in lipids and proteins in parasite-infected skin indicated by prominent Raman peak intensities was performed. This study is the first to demonstrate the application of Raman spectroscopy for the detection of T. brucei by targeting the skin of the host. The technique has significant potential to discriminate between infected and non-infected tissue and could represent a unique, non-invasive diagnostic tool in the goal for elimination of gambiense-HAT as well as for Animal African Trypanosomiasis (AAT).