ArticleCellular & molecular immunology2022
DOCK2 regulates antifungal immunity by regulating RAC GTPase activity.
Article in Cellular & molecular immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Human inborn errors of the phagocyte respiratory burst: Chronic granulomatous disease and beyond.Journal of human immunity · 2026Article
- DOCK1 inhibitor Box5 (TFA) suppresses proliferation of AML cell lines and prolongs survival in AML xenograft models.Scientific reports · 2026Article
- Immune-related actinopathies at the cross-road of immunodeficiency, autoimmunity and autoinflammation.Nature reviews. Immunology · 2026Review
- Advancements in nanomedicine for the therapeutic regulation of efferocytosis: opportunities and challenges.Theranostics · 2026Review
- DOCK2 modulates immune checkpoint inhibitor responsiveness and prognosis in cutaneous melanoma through multi-omics and single-cell T cell dynamics profiling.Discover oncology · 2025Article
- NIF inhibits the ability of PMNs to produce inflammatory cytokines and reactive oxygen species in response toMicrobiology spectrum · 2025Article
- Guanine Nucleotide Exchange Factors and Small GTPases: Their Regulation and Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- EPHA5 regulates antifungal innate immunity by phosphorylating EPHB2 and Dectin-1.PLoS pathogens · 2025Article
- Lipid droplets restrict phagosome formation in antifungal immunity.Cellular & molecular immunology · 2025Article
- Systemic infection by Candida albicans requires FASN-α subunit induced cell wall remodeling to perturb immune response.PLoS pathogens · 2025Article
- Inhibition of RAC1 activator DOCK2 ameliorates cholestatic liver injury via regulating macrophage polarisation and hepatic stellate cell activation.Biology direct · 2025Article
- DOCK8 gene mutation alters cell subsets, BCR signaling, and cell metabolism in B cells.Cell death & disease · 2024Article
- Linking Adiposity to Interstitial Lung Disease: The Role of the Dysfunctional Adipocyte and Inflammation.Cells · 2023Review
- Multiple Immune Defects in Two Patients with Novel DOCK2 Mutations Result in Recurrent Multiple Infection Including Live Attenuated Virus Vaccine.Journal of clinical immunology · 2023Article
- Psychrophilic phage VSW-3 RNA polymerase reduces both terminal and full-length dsRNA byproducts inRNA biology · 2022Article
- The roles of fungus in CNS autoimmune and neurodegeneration disorders.Frontiers in immunology · 2022Review
- Insights from DOCK2 in cell function and pathophysiology.Frontiers in molecular biosciences · 2022Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fungal infections cause ~1.5 million deaths each year worldwide, and the mortality rate of disseminated candidiasis currently exceeds that of breast cancer and malaria. The major reasons for the high mortality of candidiasis are the limited number of antifungal drugs and the emergence of drug-resistant species. Therefore, a better understanding of antifungal host defense mechanisms is crucial for the development of effective preventive and therapeutic strategies. Here, we report that DOCK2 (dedicator of cytokinesis 2) promotes indispensable antifungal innate immune signaling and proinflammatory gene expression in macrophages. DOCK2-deficient macrophages exhibit decreased RAC GTPase (Rac family small GTPase) activation and ROS (reactive oxygen species) production, which in turn attenuates the killing of intracellular fungi and the activation of downstream signaling pathways. Mechanistically, after fungal stimulation, activated SYK (spleen-associated tyrosine kinase) phosphorylates DOCK2 at tyrosine 985 and 1405, which promotes the recruitment and activation of RAC GTPases and then increases ROS production and downstream signaling activation. Importantly, nanoparticle-mediated delivery of in vitro transcribed (IVT) Rac1 mRNA promotes the activity of Rac1 and helps to eliminate fungal infection in vivo. Taken together, this study not only identifies a critical role of DOCK2 in antifungal immunity via regulation of RAC GTPase activity but also provides proof of concept for the treatment of invasive fungal infections by using IVT mRNA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.