ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
TLR9 and IRF3 cooperate to induce a systemic inflammatory response in mice injected with liposome:DNA.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- A sinomenine derivative protects life-threatening inflammatory injuries via covalently binding to a novel allosteric inhibition site of IRF3.Acta pharmacologica Sinica · 2026Article
- Extracellular heme:DNA complexes promote oxidative stress and inflammation during lupus-associated hemolysis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Interferon Regulatory Factor 3 Exacerbates the Severity of COVID-19 in Mice.Critical care explorations · 2025Article
- IRF3 Signaling within the Mouse Stroma Influences Sepsis Pathogenesis.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Aged IRF3-KO Mice are Protected from Sepsis.Journal of inflammation research · 2021Article
- The Role of Nucleic Acid Sensing in Controlling Microbial and Autoimmune Disorders.International review of cell and molecular biology · 2019Review
- Circadian Rhythms Influence the Severity of Sepsis in Mice via a TLR2-Dependent, Leukocyte-Intrinsic Mechanism.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Increased expression of endosomal members of toll-like receptor family abrogates wound healing in patients with type 2 diabetes mellitus.International wound journal · 2016Article
- Possible role of TLR4 and TLR9 SNPs in protection against congenital toxoplasmosis.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2015Article
- Evaluation of gene delivery strategies to efficiently overexpress functional HLA-G on human bone marrow stromal cells.Molecular therapy. Methods & clinical development · 2014Article
- IRF3 contributes to sepsis pathogenesis in the mouse cecal ligation and puncture model.Journal of leukocyte biology · 2012Article
- Effects of particle size on toll-like receptor 9-mediated cytokine profiles.Biomaterials · 2011Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Liposome:DNA is a promising gene therapy vector. However, this vector can elicit a systemic inflammatory response syndrome (SIRS). Prior reports indicate that liposome:DNA vectors activate Toll-like receptor (TLR)9. We hypothesized that liposome:DNA vectors also activate the cytosolic DNA-sensing pathway, which signals via interferon (IFN) regulatory factor (IRF)3. To test this, we treated dendritic cells (DCs) with liposome:DNA in vitro and found that IRF3 was phosphorylated independent of TLR9. To test the contribution of this pathway in vivo, we injected a liposome:DNA vector into wild-type (WT), TLR9-knockout (KO), IRF3-KO, and TLR9-IRF3-double-KO (DKO) mice. WT mice exhibited a systemic inflammatory response, evidenced by elevations in serum cytokines, serum enzyme changes indicating organ damage, hypothermia, and mortality. The cytokine response was reduced in TLR9-KO, IRF3-KO, and TLR9-IRF3-DKO mice and all three groups survived. We found that IFN-gamma-KO mice that receive liposome:DNA had a reduced cytokine response and 100% survival. CD11c(+) and NK1.1(+) cells produced IFN-gamma and depleting CD11c(+) cells reduced the cytokine response in mice injected with liposome:DNA. These findings may facilitate the development of immunologically inert gene therapy vectors and may provide general insight into the mechanisms of SIRS.
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