ArticleProceedings of the National Academy of Sciences of the United States of America2024
Copper regulates the host innate immune response against bacterial infection via activation of ALPK1 kinase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 58 citations in OpenAlex.
- Disease-Stage Synchronized Nanozyme Therapy for Polymicrobial Sepsis through Adaptive Catalytic and Immune Reprogramming.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Chinese sacbrood virus destroys AcPPAN-copper homeostasis to evade phenoloxidase-based antiviral immunity in Apis cerana.BMC veterinary research · 2026Article
- Blockage of cuproplasia inhibits pancreatic tumour-associated neutrophils infiltration through TRAF6/STAT3/CCL2 pathway.British journal of cancer · 2026Article
- Copper Metabolism in Isolated Macrophages: Regulator of Immunity and Inflammation.Veterinary sciences · 2026Review
- Acetylated mitochondrial MDH2 regulates CTR2 transcription to induce cuproptosis during Escherichia coli infection.Nature communications · 2026Article
- The Two Faces of Copper Capture Driven by the Internal His/Met-Rich and N-Terminal His-Rich Domains of CopI.Inorganic chemistry · 2026Article
- Review
- Copper Dyshomeostasis, Redox Buffering and Immune Aging Converge on Cuproptosis in Age-Related Diseases.Antioxidants (Basel, Switzerland) · 2026Review
- Tudor domain-containing protein 9-targeting siRNA nanoparticles alleviate Pseudomonas aeruginosa lung injury in preclinical models by promoting neutrophil cuproptosis.Nature communications · 2026Article
- Context-dependent ATP7 Interactions with Parkinson's Disease-associated Genes Modulate Copper Homeostasis Phenotypes.bioRxiv : the preprint server for biology · 2026Article
- Cuproptosis promotes inflammatory osteolysis via GYS1-mediated glycogen metabolism.International journal of oral science · 2026Article
- Targeting RSF1 with tanshinone I inhibits cervical cancer cell growth through modulation of NF-κB pathway.Frontiers in pharmacology · 2026Article
- From Fungicide to Phagosome: A One Health View of Copper-Driven Fungal-Bacterial Interactions.Current clinical microbiology reports · 2026Review
- Bcl-2 inhibitor resistance in diffuse large b-cell lymphoma: establishing a prognostic signature and targeting alpha protein kinase 1.Frontiers in oncology · 2026Article
- Tumor immune microenvironment score predicts efficacy of immune checkpoint inhibitors-based regimens in advanced non-small cell lung cancer.Journal of translational medicine · 2025Article
- The CueR-regulated transporters CopA and CusFABC coordinate copper detoxification inVirulence · 2025Article
- Copper homeostasis and cuproptosis in Alzheimer's disease (Review).International journal of molecular medicine · 2025Review
- Dual-responsive copper complex delivered by dissolvable microneedle promotes polymicrobial infection eradication and cutaneous wound healing.Materials today. Bio · 2025Article
- Multivalent Immune-Protective Effects of Egg Yolk Immunoglobulin Y (IgY) Derived from Live or InactivatedInternational journal of molecular sciences · 2025Article
- Potential Therapeutic Effect of ZnO/CuO Nanocomposite as an Acaricidal, Immunostimulant, and Antioxidant in Rabbits.Veterinary sciences · 2025Article
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Authors and funding
11 authors at 2 institutions in 3 countries.
Funding
Abstract
Copper is an essential trace element for the human body, and its requirement for optimistic immune functions has been recognized for decades. How copper is involved in the innate immune pathway, however, remains to be clarified. Here, we report that copper serves as a signal molecule to regulate the kinase activity of alpha-kinase 1 (ALPK1), a cytosolic pattern-recognition receptor (PRR), and therefore promotes host cell defense against bacterial infection. We show that in response to infection, host cells actively accumulate copper in the cytosol, and the accumulated cytosolic copper enhances host cell defense against evading pathogens, including intracellular and, unexpectedly, extracellular bacteria. Subsequently, we demonstrate that copper activates the innate immune pathway of host cells in an ALPK1-dependent manner. Further mechanistic studies reveal that copper binds to ALPK1 directly and is essential for the kinase activity of this cytosolic PRR. Moreover, the binding of copper to ALPK1 enhances the sensitivity of ALPK1 to the bacterial metabolite ADP-heptose and eventually prompts host cells to elicit an enhanced immune response during bacterial infection. Finally, using a zebrafish in vivo model, we show that a copper-treated host shows an increased production of proinflammatory cytokines, enhanced recruitment of phagosome cells, and promoted bacterial clearance. Our findings uncover a previously unrecognized role of copper in the modulation of host innate immune response against bacterial pathogens and advance our knowledge on the cross talk between cytosolic copper homeostasis and immune system.
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