The role of TLR9 on Leishmania amazonensis infection and its influence on intranasal LaAg vaccine efficacy

PLoS Neglected Tropical Diseases
Juliana Elena Silveira PrattiHerbert Leonel De Matos Guedes

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, analys...Continue Reading

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Citations

Oct 22, 2019·Human Vaccines & Immunotherapeutics·Beatriz Coutinho De OliveiraValéria Rêgo Alves Pereira
Jan 29, 2020·Medical Mycology·Lívia S RamosAndré L S Santos
Jan 16, 2021·Scientific Reports·Elias Barbosa da Silva-JuniorCelio Geraldo Freire-de-Lima
May 4, 2021·The Journal of Pharmacy and Pharmacology·Deepender KaushikDeepak B Salunke

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Methods Mentioned

BETA
optical microscopy
flow cytometry
ELISA
PMA

Software Mentioned

FlowJo X
Cell F
GraphPad Prism

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