Extracellular Vesicles from Contribute in Stimulating Immune Response and Immunosuppression in Hosts with Visceral Leishmaniasis

Overview

Journal Microorganisms

Specialty Microbiology

Date 2024 Feb 24

PMID 38399674

Authors

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

Affiliations

Soon will be listed here.

Abstract

Visceral leishmaniasis (VL) is a chronic systemic disease. In Brazil this infection is caused by . Extracellular vesicles (EVs) released by species have different functions like the modulation of host immune systems and inflammatory responses, among others. This study evaluated the participation of EVs from (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 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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