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Background <p>Leishmaniasis, a parasitic disease caused by <i>Leishmania</i> protozoa, has various clinical forms and is endemic in Brazil. Traditional experimental infection methods using intradermal and subcutaneous needles do not resemble natural sand fly transmission and are associated with risks of laboratory accidents owing to the use of low-gauge needles. In this study, we investigated the application of microneedles for transdermal (TD) infections to better replicate the deposition of parasites observed in the natural infection environment while ensuring safe handling in the laboratory.</p> Methods <p>Initial experiments involved inducing TD infections using 1-, 7- or 12-microneedle cartridges, compared with inducing conventional intradermal (ID) infections in the ears of BALB/c mice. Subsequent tests used a 12-microneedle cartridge at different tissue depths (0.25, 0.5, 0.75, 1.0 and 1.5&#xa0;mm), followed by challenge with different doses of <i>Leishmania amazonensis</i>. In addition, histology and flow cytometry studies were performed 30&#xa0;min post-infection.</p> Results <p>Transdermal infections produced similar lesion development and parasite loads as ID infections. More tissue destruction was induced using the 1- or 7-microneedle cartridge compared to the 12-microneedle cartridge and ID infection. Infection was successfully established at all microneedle depths (0.25, 0.5, 0.75 and 1.0&#xa0;mm), resulting in comparable lesion thickness across the different experimental groups, with no statistically significant differences observed. The parasite load and lesion thickness were dependent on the inoculum size in the ear infection via the TD route, with efficient lesion progression using 2 × 10<sup>6</sup> and 2 × 10<sup>5</sup> promastigotes. Parasite loads in the ear were similar between the two approaches at the early stages, specifically at 30&#xa0;min and 12&#xa0;h post-infection. Thirty minutes post-infection, cytometry analysis indicated recruitment of neutrophils to the lesion site, regardless of the infection model used. The TD model specifically attracted neutrophils, independent of the presence of parasites.</p> Conclusions <p>This novel microneedle infection model enables efficient challenge and reduces risks during animal experimentation. This technique holds promise for future studies of leishmaniasis therapy and vaccine development.</p> Graphical Abstract <p></p>

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Establishment of a transdermal infection model with Leishmania amazonensis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月22日

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  • Naiara Carla Manhães,
  • Hozany Praxedes,
  • Alisson Amaral Da-Rocha,
  • Douglas Barroso de Almeida,
  • Igor Bittencourt dos Santos,
  • Elias Barbosa da Silva-Junior,
  • Luciana Covre,
  • Celio Geraldo Freire-de-Lima,
  • Daniel Claudio Oliveira Gomes,
  • Alda M. da-Cruz,
  • Alessandra Marcia da Fonseca-Martins,
  • Herbert Leonel de Matos Guedes

摘要

Background

Leishmaniasis, a parasitic disease caused by Leishmania protozoa, has various clinical forms and is endemic in Brazil. Traditional experimental infection methods using intradermal and subcutaneous needles do not resemble natural sand fly transmission and are associated with risks of laboratory accidents owing to the use of low-gauge needles. In this study, we investigated the application of microneedles for transdermal (TD) infections to better replicate the deposition of parasites observed in the natural infection environment while ensuring safe handling in the laboratory.

Methods

Initial experiments involved inducing TD infections using 1-, 7- or 12-microneedle cartridges, compared with inducing conventional intradermal (ID) infections in the ears of BALB/c mice. Subsequent tests used a 12-microneedle cartridge at different tissue depths (0.25, 0.5, 0.75, 1.0 and 1.5 mm), followed by challenge with different doses of Leishmania amazonensis. In addition, histology and flow cytometry studies were performed 30 min post-infection.

Results

Transdermal infections produced similar lesion development and parasite loads as ID infections. More tissue destruction was induced using the 1- or 7-microneedle cartridge compared to the 12-microneedle cartridge and ID infection. Infection was successfully established at all microneedle depths (0.25, 0.5, 0.75 and 1.0 mm), resulting in comparable lesion thickness across the different experimental groups, with no statistically significant differences observed. The parasite load and lesion thickness were dependent on the inoculum size in the ear infection via the TD route, with efficient lesion progression using 2 × 106 and 2 × 105 promastigotes. Parasite loads in the ear were similar between the two approaches at the early stages, specifically at 30 min and 12 h post-infection. Thirty minutes post-infection, cytometry analysis indicated recruitment of neutrophils to the lesion site, regardless of the infection model used. The TD model specifically attracted neutrophils, independent of the presence of parasites.

Conclusions

This novel microneedle infection model enables efficient challenge and reduces risks during animal experimentation. This technique holds promise for future studies of leishmaniasis therapy and vaccine development.

Graphical Abstract