Projects per year
Abstract / Description of output
The role of mitochondria in immunity is increasingly recognized, but it is unclear how variation in mitochondrial DNA (mtDNA) contributes to variable infection outcomes. To quantify the effect of mtDNA variation on humoral and cell-mediated innate immune responses, we utilized a panel of fruit fly Drosophila melanogaster cytoplasmic hybrids (cybrids), where unique mtDNAs (mitotypes) were introgressed into a controlled isogenic nuclear background. We observed substantial heterogeneity in infection outcomes within the cybrid panel upon bacterial, viral and parasitoid infections, driven by the mitotype. One of the mitotypes, mtKSA2 protected against bacterial, parasitoid, and to a lesser extent, viral infections. Enhanced survival was not a result of improved bacterial clearance, suggesting mtKSA2 confers increased disease tolerance. Transcriptome sequencing showed that the mtKSA2 mitotype had an upregulation of genes related to mitochondrial respiration and phagocytosis in uninfected flies. Upon infection, mtKSA2 flies exhibited infection type and duration specific transcriptomic changes. Furthermore, uninfected mtKSA2 larvae showed immune activation of hemocytes (immune cells), increased hemocyte numbers and ROS production, and enhanced encapsulation response against parasitoid wasp eggs and larvae. Our results show that mtDNA variation acts as an immunomodulatory factor in both humoral and cell-mediated innate immunity and that specific mitotypes can provide broad protection against infections.
Original language | English |
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Article number | e1011476 |
Number of pages | 37 |
Journal | PLoS Genetics |
Volume | 20 |
Issue number | 11 |
Early online date | 11 Nov 2024 |
DOIs | |
Publication status | E-pub ahead of print - 11 Nov 2024 |
Keywords / Materials (for Non-textual outputs)
- AMP
- CFU
- Drosophila
- hemocyte
- innate immunity
- Leptopilina boulardi
- OXPHOS
- pathogen
- ROS
- resistance
- RNA sequencing
- tolerance
- transcriptomics
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Dive into the research topics of 'A naturally occurring mitochondrial genome variant confers broad protection from infection in Drosophila'. Together they form a unique fingerprint.Projects
- 3 Finished
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Underpinning UK Bioscience Research with high-throughput single molecule sequencing
Keightley, P., Connelley, T., Macqueen, D., Prendergast, J., Santoyo-Lopez, J., Smith, J., Twyford, A. & Watson, M.
10/11/20 → 9/04/21
Project: Research
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NERC BIOMOLECULAR ANALYSIS FACILITY - EDINBURGH
Twyford, A. & Blaxter, M.
1/04/18 → 31/03/21
Project: Research
Datasets
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Data and code for: A naturally occurring mitochondrial genome variant confers broad protection from infection in Drosophila (doi: https://doi.org/10.1101/2024.03.28.587162)
Salminen, T. (Creator), Vesala, L. (Creator), Basikhina, Y. (Creator), Kutzer, M. (Creator), Tuomela, T. (Creator), Lucas, R. (Creator), Monteith, K. (Creator), Prakash, A. (Creator), Tietz, T. (Creator) & Vale, P. (Creator), Zenodo, 5 Sept 2024
Dataset