ArticlePLoS neglected tropical diseases2019
The role of TLR9 on Leishmania amazonensis infection and its influence on intranasal LaAg vaccine efficacy.
Article in PLoS neglected tropical diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Revisiting the past in light of current knowledge on γδ T cells in leishmaniasis.Frontiers in immunology · 2026Review
- Leishmaniasis: pathogenesis, host immunity, and the evolving landscape of immunotherapy and immunochemotherapy.Frontiers in microbiology · 2026Review
- Leishmania amazonensis infection induces PD-L1 expression on dendritic cells and impairs Th1 responses in vitro and in vivo.Scientific reports · 2025Article
- Roles of TLR9: Gatekeeper to fungal infections.PLoS pathogens · 2025Article
- Designing of a new multi-epitope vaccine against Leishmania major using Leish-F1 epitopes: An In-silico study.PloS one · 2024Article
- Crosslinked chitosan microparticles as a safe and efficient DNA carrier for intranasal vaccination against cutaneous leishmaniasis.Vaccine: X · 2023Article
- Toll-like Receptor-9 (TLR-9) Signaling Is Crucial for Inducing Protective Immunity following Immunization with Genetically Modified Live AttenuatedPathogens (Basel, Switzerland) · 2023Article
- Pulmonary Fibrosis and Hypereosinophilia in TLR9Pathogens (Basel, Switzerland) · 2022Article
- Article
- Paradoxical immune response in leishmaniasis: The role of toll-like receptors in disease progression.Parasite immunology · 2022Review
- Intranasal vaccine from whole Leishmania donovani antigens provides protection and induces specific immune response against visceral leishmaniasis.PLoS neglected tropical diseases · 2021Article
- The role of Toll-like receptor 9 in a murine model of Cryptococcus gattii infection.Scientific reports · 2021Article
- The Paradox of a Phagosomal Lifestyle: How Innate Host Cell-Frontiers in immunology · 2021Review
- Vaccines for leishmaniasis and the implications of their development for American tegumentary leishmaniasis.Human vaccines & immunotherapeutics · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leishmania (L.) amazonensis is one of the etiological agents of cutaneous leishmaniasis (CL) in Brazil. Currently, there is no vaccine approved for human use against leishmaniasis, although several vaccine preparations are in experimental stages. One of them is Leishvacin, or LaAg, a first-generation vaccine composed of total L. amazonensis antigens that has consistently shown an increase of mouse resistance against CL when administered intranasally (i.n.). Since Toll-like receptor 9 (TLR9) is highly expressed in the nasal mucosa and LaAg is composed of TLR9-binding DNA CpG motifs, in this study we proposed to investigate the role of TLR9 in both L. amazonensis infection and in LaAg vaccine efficacy in C57BL/6 (WT) mice and TLR9-/- mice. First, we evaluated, the infection of macrophages by L. amazonensis in vitro, showing no significant difference between macrophages from WT and TLR9-/- mice in terms of both infection percentage and total number of intracellular amastigotes, as well as NO production. In addition, neutrophils from WT and TLR9-/- mice had similar capacity to produce neutrophil extracellular traps (NETs) in response to L. amazonensis. L. amazonensis did not activate dendritic cells from WT and TLR9-/- mice, analysed by MHCII and CD86 expression. However, in vivo, TLR9-/- mice were slightly more susceptible to L. amazonensis infection than WT mice, presenting a larger lesion and an increased parasite load at the peak of infection and in the chronic phase. The increased TLR9-/- mice susceptibility was accompanied by an increased IgG and IgG1 production; a decrease of IFN-γ in infected tissue, but not IL-4 and IL-10; and a decreased number of IFN-γ producing CD8+ T cells, but not CD4+ T cells in the lesion-draining lymph nodes. Also, TLR9-/- mice could not control parasite growth following i.n. LaAg vaccination unlike the WT mice. This protection failure was associated with a reduction of the hypersensitivity response induced by immunization. The TLR9-/- vaccinated mice failed to respond to antigen stimulation and to produce IFN-γ by lymph node cells. Together, these results suggest that TLR9 contributes to C57BL/6 mouse resistance against L. amazonensis, and that the TLR9-binding LaAg comprising CpG motifs may be important for intranasal vaccine efficacy against CL.
Indexed as
Identifiers
What OpenQuestion holds
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.