Molecular analysis of human tick-bitten skin yields signatures associated with distinct spatial and temporal trajectories - A proof-of-concept study

Wenna Lee; Rym Ben-Othman; Patrycja Skut; Amy Huey-Yi Lee; Amanda D Barbosa; Miles Beaman; Andrew Currie; Nathan T Harvey; Prasad Kumarasinghe; Roy A Hall; James Potter; Stephen Graves; Nicholas P West; Amanda J Cox; Peter J Irwin; Tobias R Kollmann; Charlotte L Oskam

doi:10.1016/j.heliyon.2024.e33600

Molecular analysis of human tick-bitten skin yields signatures associated with distinct spatial and temporal trajectories - A proof-of-concept study

Heliyon. 2024 Jun 29;10(13):e33600. doi: 10.1016/j.heliyon.2024.e33600. eCollection 2024 Jul 15.

Authors

Wenna Lee^{1

2

3}, Rym Ben-Othman², Patrycja Skut², Amy Huey-Yi Lee⁴, Amanda D Barbosa^{1

5

6}, Miles Beaman⁷, Andrew Currie^{3

8}, Nathan T Harvey^{7

9}, Prasad Kumarasinghe^{10

11

12}, Roy A Hall¹³, James Potter¹³, Stephen Graves¹⁴, Nicholas P West¹⁵, Amanda J Cox¹⁵, Peter J Irwin⁵, Tobias R Kollmann², Charlotte L Oskam^{1

3}

Affiliations

¹ Centre for Biosecurity and One Health, Harry Butler Institute, Murdoch University, Murdoch, WA, Australia.
² Telethon Kids Institute, Perth, WA, Australia.
³ School of Medical, Molecular, and Forensic Sciences, College of Environmental and Life Sciences, Murdoch University, Murdoch, WA, Australia.
⁴ Molecular Biology and Biochemistry, Simon Fraser University, British Columbia, Canada.
⁵ School of Veterinary Medicine, College of Environmental and Life Sciences, Murdoch University, Murdoch, WA, Australia.
⁶ CAPES Foundation, Ministry of Education of Brazil, Brasilia, DF, Brazil.
⁷ Faculty of Health and Medical Sciences, Pathology & Laboratory Medicine, University of Western Australia, Perth, WA, Australia.
⁸ Centre for Molecular Medicine and Innovative Therapeutics, Health Futures Institute, Murdoch University, Murdoch, WA, Australia.
⁹ Department of Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Perth, WA, Australia.
¹⁰ School of Medicine, University of Western Australia, Crawley, WA, Australia.
¹¹ College of Science, Health, Education and Engineering, Murdoch University, Murdoch, WA, Australia.
¹² Western Dermatology, Hollywood Medical Centre, Nedlands, WA, Australia.
¹³ Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia.
¹⁴ Australian Rickettsial Reference Laboratory, Barwon Health, Geelong, VIC, Australia.
¹⁵ School of Pharmacy and Medical Sciences, and Menzies Health Institute, Griffith University, QLD, Australia.

Abstract

Tick-associated diseases present challenges due to tridirectional interactions among host-specific responses, tick toxins and salivary proteins as well as microbes. We aimed to uncover molecular mechanisms in tick-bitten skin samples (cases) and contralateral skin samples (controls) collected simultaneously from the same participants, using spatial transcriptomics. Cases and controls analysed using NanoString GeoMx Digital Spatial Profiler identified 274 upregulated and 840 downregulated differentially expressed genes (DEGs), revealing perturbations in keratinization and immune system regulation. Samples of skin biopsies taken within 72 h post tick-bite DEGs had changes in protein metabolism and viral infection pathways as compared to samples taken 3 months post tick-bite, which instead displayed significant perturbations in several epigenetic regulatory pathways, highlighting the temporal nature of the host response following tick bites. Within-individual signatures distinguished tick-bitten samples from controls and identified between-individual signatures, offering promise for future biomarker discovery to guide prognosis and therapy.

Keywords: Emerging diseases; Spatial profiling; Spatial transcriptomics; Tick-borne diseases; Tick-host-pathogen.