Dados do Trabalho

Título

Intranasal immunization with Leishmania amazonensis extracellular vesicles induced a protective immune response in BALB/c mice

Introdução

Leishmaniasis is a group of diseases caused by Leishmania spp. Currently, there are no vaccines available to prevent human disease, and patients are treated with drugs with high toxicity. Our group showed that extracellular vesicles (EVs) released by Leishmania amazonensis induced a partial protective immune response in mice intraperitoneally immunized. EVs are particles with a bilipid bilayer released by prokaryotic and eukaryotic cells. They carry proteins, lipids, DNA, and/or RNA and participate in cell-to-cell communication. Further investigation of the immunological properties of Leishmania EVs may contribute to develop a highly effective leishmaniasis vaccine. 

Objetivo (s)

Evaluation of the intranasal administration of L. amazonensis EVs for triggering of a protective immune response against the parasite.

Material e Métodos

BALB/c mice were intranasally immunized with 4 μg of EVs released by L. amazonensis promastigotes with different virulence profiles (LT-P - attenuated and IVD-P - virulent profiles). After 15 days of the second immunization, the animals were subcutaneously challenged on the hind paw with L. amazonensis promastigotes (IVD-P). The work was approved by the Ethics Committee of UNIFESP (CEUA 9287250422). 

Resultados e Conclusão

Animals immunized with L. amazonensis EVs produced specific antibodies anti-EVs. In addition, we observed a higher production of IFN-g and TNF-α cytokines in animals immunized with EVs from LT-P. After challenge with the virulent parasite, the group immunized with EVs from parasites with LT-P profile showed a significantly lower lesion and lower parasite load compared to the group immunized with EVs obtained from parasites with IVD-P profile and group of non-immunized animals (P<0.05). The histological analysis of the lesion showed a significant reduction in inflammatory response in animals immunized with EVs from LT-P (P<0.001). In addition, EVs from LT-P stimulated a significantly higher level of IFN-g, TNF-α, and IL-6 compared to the groups immunized with EVs of IVD-P and non-immunized mice (P<0.01). We detected in the lung tissue a significant increase in the expression of Toll-like receptor (TLR) 2, TLR-6, and TLR-9 in animals intranasally immunized with LT-P EVs as compared to the control group. Conclusion: Our results showed that the intranasal immunization with L. amazonensis EVs is promising and may trigger a protective response to L. amazonensis infection.

Palavras Chave

extracellular vesicles; Leishmania amazonensis; intranasal immunization