Microorganisms (Jan 2024)

Extracellular Vesicles from <i>Leishmania (Leishmania) infantum</i> Contribute in Stimulating Immune Response and Immunosuppression in Hosts with Visceral Leishmaniasis

  • Francieli Marinho Carneiro,
  • Allecineia Bispo da Cruz,
  • Marta Marques Maia,
  • Noemi Nosomi Taniwaki,
  • Ingrid de Siqueira Pereira,
  • Gislene Mitsue Namiyama,
  • Ricardo Gava,
  • Roberto Mitsuyoshi Hiramoto,
  • Bruno Vicente,
  • Victor Midlej,
  • Rafael Meyer Mariante,
  • Vera Lucia Pereira-Chioccola

DOI
https://doi.org/10.3390/microorganisms12020270
Journal volume & issue
Vol. 12, no. 2
p. 270

Abstract

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Visceral leishmaniasis (VL) is a chronic systemic disease. In Brazil this infection is caused by Leishmania (Leishmania) infantum. Extracellular vesicles (EVs) released by Leishmania species have different functions like the modulation of host immune systems and inflammatory responses, among others. This study evaluated the participation of EVs from L. (L.) infantum (Leish-EVs) in recognition of the humoral and cellular immune response of hosts with VL. Promastigotes were cultivated in 199 medium and, in the log phase of growth, they were centrifuged, washed, resus-pended in RPMI medium, and incubated for 2 to 24 h, at 25 °C or 37 °C to release Leish-EVs. This dynamic was evaluated using transmission (TEM) and scanning (SEM) electron microscopies, as well as nanoparticle tracking analysis (NTA). The results suggested that parasite penetration in mammal macrophages requires more Leish-EVs than those living in insect vectors, since promastigotes incubated at 37 °C released more Leish-EVs than those incubated at 25 °C. Infected THP-1 cells produced high EV concentration (THP-1 cells-EVs) when compared with those from the control group. The same results were obtained when THP-1 cells were treated with Leish-EVs or a crude Leishmania antigen. These data indicated that host–EV concentrations could be used to distinguish infected from uninfected hosts. THP-1 cells treated with Leish-EVs expressed more IL-12 than control THP-1 cells, but were unable to express IFN-γ. These same cells highly expressed IL-10, which inhibited TNF-α and IL-6. Equally, THP-1 cells treated with Leish-EVs up-expressed miR-21-5p and miR-146a-5p. In conclusion, THP-1 cells treated with Leish-EVs highly expressed miR-21-5p and miR-146a-5p and caused the dysregulation of IL-10. Indirectly, these results suggest that high expression of these miRNAs species is caused by Leish-EVs. Consequently, this molecular via can contribute to immunosuppression causing enhanced immunopathology in infected hosts.

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