«Leishmania» parasites and the host macrophage: Interaction via secretion
Notice bibliographique
Résumé
Protozoan parasites of genus Leishmania are the causative agents of leishmaniasis. Utilizing potent immune evasion and immune modulation mechanisms, Leishmania are able to render the host macrophage inactive and live inside its phagolysosome. Studies on the different functions of secreted vesicles, especially exosomes, which are secreted vesicles of less than 100nm in size, have now established them as an important route for cell-cell communication, in both homeostasis and pathogenesis. In this thesis, we evaluated the role of the exoproteome and exosomes in the host-parasite interactions of Leishmania. We observed that protein and exovesicle release is augmented in Leishmania mexicana following temperature shift (TS), a condition mimicking parasite's entry into its mammalian host. We next showed that TS-induced exoproteome of L. mexicana has various inhibitory properties such as induction of protein tyrosine phosphatase (PTP) activity, and inhibition of nitric oxide (NO) production. Having seen the augmentation in vesicle release in response to TS, we next specifically examined the immune modulation by Leishmania exosomes, which are secreted vesicles of smaller than 100nm in size. We compared the immunomodulatory properties of parasites and exosomes knocked out (KO) for GP63, a critical virulence factor of Leishmania, with their wildtype (WT) Leishmania major counterparts. Looking at PTPs, transcription factors, gene expression and also in vivo inflammatory recruitment, we observed that absence of GP63 results in a stronger inflammatory response to both L. major parasites and exosomes. Especially, we observed downregulation of expression of many immune receptors and adaptors following L. major infection. Also, we found WT and KO exosomes to have drastic differences in their protein content, suggesting a novel role for GP63 in exosomal protein sorting. Finally, we investigated the effect of Leishmania infection on exosome release by macrophages. For this purpose, we performed comparative proteomic analyses of exosomes released from nontreated macrophages, LPS-stimulated macrophages and L. mexicana¬-infected macrophages. We observed that Leishmania infection and LPS stimulation induce similar and also distinct alterations in the sorting of different protein functional groups into exosomes, especially those associated with the plasma membrane. These alterations can potentially change the effector functions as well as targeting of exosomes. Consequently, we observed that these exosomes differentially induce signaling molecules such as MAP Kinases in naive macrophages. Overall, we provide a new insight on the role of exosomes in the Leishmania host-parasite interactions, especially in the establishment of infection. We also expanded the understanding of the immune modulation mechanisms by Leishmania GP63. Our results deepen the knowledge regarding leishmaniasis and pave the way for development of new therapeutics.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».