Chapitre VI : Conclusion générale et perspectives
6.5. Futures orientations
L'utilisation du modèle animal d'infection de M. ulcerans que nous avons mis au point a permis d'acquérir de nouvelles connaissances sur la pathogénie de l'UB. Cependant, du fait que le système immunologique de la souris soit fondamentalement différent de celui de l'humain [285], les résultats que nous avons obtenus, ne peuvent pas être transférés directement chez l'humain. De même, notre travail étant un travail pionnier dans le domaine, nos conclusions débouchent sur plusieurs pistes de recherche. Par exemple :
S Estce que les cellules musculaires (cellules satellites) sont plus sensibles à la mycolactone que les autres types cellulaires (ex. fibroblastes, cellules endothéliales).
S Estce que les fibres lentes ou rapides pourraient être plus vulnérables à l'action nécrotique de la mycolactone ?
S Estce que la mycolactone empêche la conversion des macrophages pro inflammatoires vers des macrophages antiinflammatoires ?
S L'atrophie des tissus musculaires estelle causée principalement par une diminution de la synthèse ou par une augmentation de la dégradation des protéines musculaires?
S Par quels mécanismes moléculaires la mycolactone et/ou le M. ulcerans provoquentils la lyse des protéines musculaires et la régénération imparfaite du muscle squelettique ?
■S Le muscle squelettique humain présenteil des dommages semblables à ceux observés dans notre modèle animal ?
S Quel sera alors, le programme de réadaptation à mettre en œuvre en vue de prévenir et/ou de réduire les séquelles fonctionnelles engendrées par la maladie et à quel moment ? Ees ébauches d'un tel protocole sont présentées au point 6.4.2 précédent.
Enfin sans être exhaustif, l'évaluation de la dégénérescence et de la régénération musculaires associées à l'infection à M. ulcerans suscitent à l'étape actuelle, d'intéressantes interrogations que nous pensons aborder dans un avenir très proche.
_ 23
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Fig. annexes 1 : Amplitude de la variation de l'EFN-y et de I'LL-10 dans le sang de souris C57BL/6 infectée de M. ulcerans. Exs valeurs sont des moyennes ± erreur standard moyenne (n =5 expérimentations distinctes). * Significativement différent de 7 jours ; # Significativement différente de 21 jours. P < 0,05.
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