Mitochondrial perturbation in immune cells enhances cell-mediated innate immunity in Drosophila

• Published in: BMC biology Vol. 22; no. 1; p. 60
• Main Authors: Vesala, Laura, Basikhina, Yuliya, Tuomela, Tea, Nurminen, Anssi, Siukola, Emilia, Vale, Pedro F, Salminen, Tiina S
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 13.03.2024; BioMed Central; BMC
• Subjects: Aerobic glycolysis; Analysis; Animals; Apoptosis; Autophagy; Cell activation; Cell-mediated immunity; Chronic fatigue syndrome; Control; Depolarization; Drosophila; Drosophila melanogaster - metabolism; Energy metabolism; Fat body; Females; Fruit flies; Genes; Genetic aspects; Health aspects; Hemocyte; Hemocytes; Hemocytes - metabolism; Humans; Identification and classification; Immune response; Immune system; Immunity (Disease); Immunity, Innate; Immunocompetence; Infection; Infections; Innate immunity; Insects; Lamellocyte; Leptopilina boulardi; Membrane potential; Metabolism; Metabolites; Mitochondria; Mitochondrial DNA; Mitochondrial membrane potential; Mitochondrial unfolded protein response; Nodules; Oxidative phosphorylation; Perturbation; Phosphorylation; Physiological aspects; Protein folding; Reactive oxygen species; RNA sequencing; UQCR-C1; Wasps; Wasps - genetics; United Kingdom; UQCR-C1; Infection; RNA sequencing; Reactive oxygen species; Leptopilina boulardi; Hemocyte; Lamellocyte; Oxidative phosphorylation; Aerobic glycolysis; Mitochondrial unfolded protein response; Mitochondrial membrane potential
• ISSN: 1741-7007; 1741-7007
• DOI: 10.1186/s12915-024-01858-5

Mitochondria participate in various cellular processes including energy metabolism, apoptosis, autophagy, production of reactive oxygen species, stress responses, inflammation and immunity. However, the role of mitochondrial metabolism in immune cells and tissues shaping the innate immune responses are not yet fully understood. We investigated the effects of tissue-specific mitochondrial perturbation on the immune responses at the organismal level. Genes for oxidative phosphorylation (OXPHOS) complexes cI-cV were knocked down in the fruit fly Drosophila melanogaster, targeting the two main immune tissues, the fat body and the immune cells (hemocytes). While OXPHOS perturbation in the fat body was detrimental, hemocyte-specific perturbation led to an enhanced immunocompetence. This was accompanied by the formation of melanized hemocyte aggregates (melanotic nodules), a sign of activation of cell-mediated innate immunity. Furthermore, the hemocyte-specific OXPHOS perturbation induced immune activation of hemocytes, resulting in an infection-like hemocyte profile and an enhanced immune response against parasitoid wasp infection. In addition, OXPHOS perturbation in hemocytes resulted in mitochondrial membrane depolarization and upregulation of genes associated with the mitochondrial unfolded protein response. Overall, we show that while the effects of mitochondrial perturbation on immune responses are highly tissue-specific, mild mitochondrial dysfunction can be beneficial in immune-challenged individuals and contributes to variation in infection outcomes among individuals.