Extracellular vesicles from Leishmania (Leishmania) infantum contribute to stimulate the 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:10.20944/preprints202312.0524.v1

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preprints.org > biology and life sciences > parasitology > doi: 10.20944/preprints202312.0524.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Extracellular vesicles from Leishmania (Leishmania) infantum contribute to stimulate the 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

Version 1 : Received: 1 December 2023 / Approved: 7 December 2023 / Online: 7 December 2023 (11:42:54 CET)

A peer-reviewed article of this Preprint also exists.

Carneiro, F.M.; da Cruz, A.B.; Maia, M.M.; Taniwaki, N.N.; Pereira, I.S.; Namiyama, G.M.; Gava, R.; Hiramoto, R.M.; Vicente, B.; Midlej, V.; Mariante, R.M.; Pereira-Chioccola, V.L. Extracellular Vesicles from Leishmania (Leishmania) infantum Contribute in Stimulating Immune Response and Immunosuppression in Hosts with Visceral Leishmaniasis. Microorganisms 2024, 12, 270. Carneiro, F.M.; da Cruz, A.B.; Maia, M.M.; Taniwaki, N.N.; Pereira, I.S.; Namiyama, G.M.; Gava, R.; Hiramoto, R.M.; Vicente, B.; Midlej, V.; Mariante, R.M.; Pereira-Chioccola, V.L. Extracellular Vesicles from Leishmania (Leishmania) infantum Contribute in Stimulating Immune Response and Immunosuppression in Hosts with Visceral Leishmaniasis. Microorganisms 2024, 12, 270.

Abstract

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 modulation of host immune system, inflammatory response, among others. This study evaluated the participation of EVs from L. (L.) infantum (Leish-EVs) in stimulation of the humoral and cellular immune responses of hosts with VL. Promastigotes were cultivated in 199 medium and, in the log phase of growth, they were centrifuged, washed, resuspended in RPMI medium and incubated for 2 to 24h, at 25ºC or 37°C to release Leish-EVs. This dynamic was evaluated by 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 25ºC. In comparison to the control group, infected THP-1 cells produced a significantly higher concentration of EVs (THP-1 cells-EVs). Similar results were obtained when THP-1 cells were treated with Leish-EVs or a crude Leishmania antigen. These data suggest that the concentration of host-EVs-Can distinguish between infected and uninfected cells. THP-1 cells treated with Leish-EVs expressed more IL-12 than control THP-1 cells, but were unable to produce IFN-γ. These same cells produced IL-10, which inhibited TNF and IL-6. Equally, THP-1 cells treated with Leish-EVs up-expressed miR-21-5p and miR-146a-5p. These findings indicate that the increased levels of miR-21-5p and miR-146a-5p observed in Leish-EVs-treated-THP-1 cells lead to immunosuppression and the secretion of pro-inflammatory cytokines.

Keywords

Extracellular vesicles; Leishmania (Leishmania) infantum, THP-1 cells, Cytokines, miRNAs

Subject

Biology and Life Sciences, Parasitology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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