A naturally occurring mitochondrial genome variant confers broad protection from infection in Drosophila. Salminen, T. S., Vesala, L., Basikhina, Y., Kutzer, M., Tuomela, T., Lucas, R., Monteith, K., Prakash, A., Tietz, T., & Vale, P. F. PLOS Genetics, 20(11):e1011476, November, 2024. Publisher: Public Library of Science![A naturally occurring mitochondrial genome variant confers broad protection from infection in Drosophila [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper Paper doi abstract bibtex 7 downloads 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.
@article{salminen_naturally_2024,
title = {A naturally occurring mitochondrial genome variant confers broad protection from infection in {Drosophila}},
volume = {20},
issn = {1553-7404},
url = {https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1011476},
doi = {10.1371/journal.pgen.1011476},
abstract = {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.},
language = {en},
number = {11},
urldate = {2024-11-13},
journal = {PLOS Genetics},
author = {Salminen, Tiina S. and Vesala, Laura and Basikhina, Yuliya and Kutzer, Megan and Tuomela, Tea and Lucas, Ryan and Monteith, Katy and Prakash, Arun and Tietz, Tilman and Vale, Pedro F.},
month = nov,
year = {2024},
note = {Publisher: Public Library of Science},
pages = {e1011476},
url_paper={https://api.zotero.org/users/837863/publications/items/BKT9W8FW/file/view}
}
Downloads: 7
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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. 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