Peroxisome-mediated metabolism is required for immune response to microbial infection
Open accessAbstract
The innate immune response is critical for animal homeostasis and is conserved from invertebrates to vertebrates. This response depends on specialized cells that recognize, internalize, and destroy microbial invaders through phagocytosis. This is coupled to autonomous or non-autonomous cellular signaling via reactive oxygen species (ROS) and cytokine production. Lipids are known signaling factors in this process, as the acute phase response of macrophages is accompanied by systemic lipid changes that help resolve inflammation. We found that peroxisomes, membrane-enclosed organelles central to lipid metabolism and ROS turnover, were necessary for the engulfment of bacteria by Drosophila and mouse macrophages. Peroxisomes were also required for resolution of bacterial infection through canonical innate immune signaling. Reduced peroxisome function impaired the turnover of the oxidative burst necessary to fight infection. This impaired response to bacterial challenge affected cell and organism survival and revealed a previously unknown requirement for peroxisomes in phagocytosis and innate immunity.
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“Recently, evidence linking peroxisomes to immunometabolism (2) has been described in macrophages, wherein through cell intrinsic mechanisms peroxisomes facilitate pathogen clearance (3), cytokine release (4), and bioactive lipid-precursor mobilization (5).”
- Authors
- Di Cara, F., Sheshachalam, A., Braverman, N. E., Rachubinski, R. A., & Simmonds, A. J.
- Affiliations
- University of Alberta (CA)
- McGill University (CA)
- Corresponding author
- Simmonds, Andrew J.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 47
- Issue
- 1
- Pages
- 93-106.e7
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2737209541
- Cited by
- 155
- References
- 44
- Citations by year
- 2026: 12 · 2025: 16 · 2024: 18 · 2023: 17 · 2022: 20 · 2021: 18 · 2020: 18 · 2019: 24 · 2018: 11 · 2017: 1
- FWCI
- 6.68
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-04-17)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Invertebrate Immune Response Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- peroxisomes, innate immunity, phagocytosis, macrophages, bacterial infection, reactive oxygen species, lipid metabolism, respiratory burst, Drosophila, inflammation resolution, cytokine production, acute phase response
- MeSH terms
- Peroxisomal Targeting Signal 2 Receptor, Animals, Cells, Cultured, Drosophila melanogaster, Immunity, Innate, Macrophages, Mice, Inbred C57BL, Staphylococcal Infections, Staphylococcus aureus, Signal Transduction, Cytokines, Respiratory Burst, Reactive Oxygen Species, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Peroxisomes, Animals, Genetically Modified, Lipid Metabolism, Mice
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