ArticleGene therapy2004
IL-18 gene therapy develops Th1-type immune responses in Leishmania major-infected BALB/c mice: is the effect mediated by the CpG signaling TLR9?
Article in Gene therapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
- A DNA Prime-Inactivated Boost Regimen Enhances Immunogenicity Against Pigeon Newcastle Disease: A Comparative Study and Analysis of Synergistic Effects.Veterinary sciences · 2026Article
- The pathogenicity and virulence of Leishmania - interplay of virulence factors with host defenses.Virulence · 2022Review
- Immunogenic properties of empty pcDNA3 plasmid against zoonotic cutaneous leishmaniasis in mice.PloS one · 2022Article
- How to master the host immune system? Leishmania parasites have the solutions!International immunology · 2018Review
- Suppression of Th1 and Th17 Responses and Induction of Treg Responses by IL-18-Expressing Plasmid Gene Combined with IL-4 on Collagen-Induced Arthritis.BioMed research international · 2018Article
- Article
- Interleukin-4 Receptor Alpha: From Innate to Adaptive Immunity in Murine Models of Cutaneous Leishmaniasis.Frontiers in immunology · 2017Review
- Protein biomarkers discriminate Leishmania major-infected and non-infected individuals in areas endemic for cutaneous leishmaniasis.BMC infectious diseases · 2016Article
- An NLRP3 inflammasome-triggered Th2-biased adaptive immune response promotes leishmaniasis.The Journal of clinical investigation · 2015Article
- Comparison of Th1 and Th2 responses in non-healing and healing patients with cutaneous leishmaniasis.Reports of biochemistry & molecular biology · 2013Article
- Interleukin-18: the master regulator driving destructive and remodeling processes in the lungs of patients with chronic obstructive pulmonary disease?American journal of respiratory and critical care medicine · 2012Article
- Human macrophage response to L. (Viannia) panamensis: microarray evidence for an early inflammatory response.PLoS neglected tropical diseases · 2012Article
- Adjuvants for Leishmania vaccines: from models to clinical application.Frontiers in immunology · 2012Article
- Does T Helper Differentiation Correlate with Resistance or Susceptibility to Infection with L. major? Some Insights From the Murine Model.Frontiers in immunology · 2012Article
- Toll-like receptors in leishmania infections: guardians or promoters?Journal of parasitology research · 2012Article
- Applying TLR synergy in immunotherapy: implications in cutaneous leishmaniasis.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- Essential role for TLR9 in prime but not prime-boost plasmid DNA vaccination to activate dendritic cells and protect from lethal viral infection.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- Therapeutic effect of low-dose IL-18 combined with IL-10 on collagen-induced arthritis by down-regulation of inflammatory and Th1 responses and induction of Th2 responses.Rheumatology international · 2009Article
- Toll-like receptors and leishmaniasis.Infection and immunity · 2008Review
- Exposure to bacterial DNA before hemorrhagic shock strongly aggravates systemic inflammation and gut barrier loss via an IFN-gamma-dependent route.Annals of surgery · 2007Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IL-18 regulates either Th1 or Th2 responses depending on the cytokine microenvironment. Administration of recombinant IL-18 (rIL-18) alone does not promote Th1 response, but rather induces Th2 response and exacerbates Leishmania major infection in susceptible BALB/c mice. Here, we treated BALB/c mice with an IL-18-expressing plasmid by using a gene gun weekly after L. major infection. This gene therapy resulted in improved pathogenic process and preferential induction of Th1 responses by inducing the expression of IL-12 p40, but treatment with rIL-18 did not. Notably, simultaneous administration of rIL-18 with an empty plasmid vector rendered BALB/c mice resistant to the infection, despite the fact that treatment with either rIL-18 alone or the plasmid vector alone did not influence the susceptibility. The synergistic role of the vector with rIL-18 was found to depend on CpG motifs, which enhanced expression of proinflammatory cytokines, especially IL-12, from APCs through Toll-like receptor (TLR) 9 ligation. Treatment with methylated plasmid vector in which CpG was disrupted could no longer prevent the disease development in coadministration with rIL-18. Taken together, IL-18 gene therapy was shown to develop Th1-type protective immunity in L. major-infected BALB/c mice without the requirement of exogenous IL-12, probably via CpG-TLR9 signaling pathway.
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