Sending a message: extracellular vesicles of pathogenic protozoan parasites

Szempruch, Anthony J.; Dennison, Lauren; Kieft, Rudo; Harrington, John M.; Hajduk, Stephen L.

doi:10.1038/nrmicro.2016.110

Cited by 100 publications

(121 citation statements)

References 76 publications

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“…In this context, EVs could act as messengers capable of priming host cells to facilitate parasite infections (42). For instance, L. infantum promastigotes constitutively secrete EVs in the lumen of sandfly midgut, which contribute to the initial infective inoculum, being co-ingested with the parasite during the bite that initiates the pathology (43).…”

Section: Discussionmentioning

confidence: 99%

Leishmania infantum Exoproducts Inhibit Human Invariant NKT Cell Expansion and Activation

et al. 2017

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Leishmania infantum is one of the major parasite species associated with visceral leishmaniasis, a severe form of the disease that can become lethal if untreated. This obligate intracellular parasite has developed diverse strategies to escape the host immune response, such as exoproducts (Exo) carrying a wide range of molecules, including parasite virulence factors, which are potentially implicated in early stages of infection. Herein, we report that L. infantum Exo and its two fractions composed of extracellular vesicles (EVs) and vesicle-depleted-exoproducts (VDEs) inhibit human peripheral blood invariant natural killer T (iNKT) cell expansion in response to their specific ligand, the glycolipid α-GalactosylCeramide (α-GalCer), as well as their capacity to promptly produce IL-4 and IFNγ. Using plate-bound CD1d and α-GalCer, we found that Exo, EV, and VDE fractions reduced iNKT cell activation in a dose-dependent manner, suggesting that they prevented α-GalCer presentation by CD1d molecules. This direct effect on CD1d was confirmed by the observation that CD1d:α-GalCer complex formation was impaired in the presence of Exo, EV, and VDE fractions. Furthermore, lipid extracts from the three compounds mimicked the inhibition of iNKT cell activation. These lipid components of L. infantum exoproducts, including EV and VDE fractions, might compete for CD1-binding sites, thus blocking iNKT cell activation. Overall, our results provide evidence for a novel strategy through which L. infantum can evade immune responses of mammalian host cells by preventing iNKT lymphocytes from recognizing glycolipids in a TCR-dependent manner.

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Section: Discussionmentioning

confidence: 99%

Leishmania infantum Exoproducts Inhibit Human Invariant NKT Cell Expansion and Activation

et al. 2017

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“…Ejemplos incluyen a Leishmanias pp., Trypanosoma cruzi (causante de la enfermedad de Chagas) y T. brucei (causante de la enfermedad del sueño), flagelados como Giardia intestinalis o Trichomonas vaginalis, o apicomplejos como el agente causal de la malaria, Plasmodium spp. (4,6). Dichas vesículas servirían para transportar factores de virulencia, por lo que constituyen una excelente diana para el control de la enfermedad.…”

Section: Es/es/divulgacion-ciencia-para-todos_10/acercate-a-nuestroscunclassified

Las vesículas extracelulares en la comunicación hospedador-parásito

Marcilla¹

2018

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“…The secretome, (excreted/secreted factors), of trypanosomes is a complex mixture of proteins, carbohydrates and lipids excreted from the surface of the parasite or secreted via exocytotic vesicles by a parasite‐specific organelle called the flagellar pocket . Some of these components are implicated in T brucei evasion of host innate response and others in the virulence process .…”

Section: Introductionmentioning

confidence: 99%

Trypanosoma brucei gambiense excreted/secreted factors impair lipopolysaccharide‐induced maturation and activation of human monocyte‐derived dendritic cells

Dauchy

Contin‐Bordes

Nzoumbou‐Boko

et al. 2019

Parasite Immunology

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Trypanosoma brucei gambiense, an extracellular eukaryotic flagellate parasite, is the main etiological agent of human African trypanosomiasis (HAT) or sleeping sickness. Dendritic cells (DCs) play a pivotal role at the interface between innate and adaptive immune response and are implicated during HAT. In this study, we investigated the effects of T gambiense and its excreted/secreted factors (ESF) on the phenotype of human monocyte‐derived DCs (Mo‐DCs). Mo‐DCs were cultured with trypanosomes, lipopolysaccharide (LPS), ESF derived from T gambiense bloodstream strain Biyamina (MHOM/SD/82), or both ESF and LPS. Importantly, ESF reduced the expression of the maturation markers HLA‐DR and CD83, as well as the secretion of IL‐12, TNF‐alpha and IL‐10, in LPS‐stimulated Mo‐DCs. During mixed‐leucocyte reactions, LPS‐ plus ESF‐exposed DCs induced a non‐significant decrease in the IFN‐gamma/IL‐10 ratio of CD4 + T‐cell cytokines. Based on the results presented here, we raise the hypothesis that T gambiense has developed an immune escape strategy through the secretion of paracrine mediators in order to limit maturation and activation of human DCs. The identification of the factor(s) in the T gambiense ESF and of the DCs signalling pathway(s) involved may be important in the development of new therapeutic targets.

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Sending a message: extracellular vesicles of pathogenic protozoan parasites

Cited by 100 publications

References 76 publications

Leishmania infantum Exoproducts Inhibit Human Invariant NKT Cell Expansion and Activation

Leishmania infantum Exoproducts Inhibit Human Invariant NKT Cell Expansion and Activation

Las vesículas extracelulares en la comunicación hospedador-parásito

Trypanosoma brucei gambiense excreted/secreted factors impair lipopolysaccharide‐induced maturation and activation of human monocyte‐derived dendritic cells

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