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Cette thèse a permis de répondre à certaines questions sur le potentiel inflammatoire des archées, mais en a soulevé de nombreuses autres. Plusieurs pistes de recherche en continuité avec les résultats obtenus dans cette thèse sont proposées dans ce chapitre.

La réponse immunitaire à diverses espèces d’archées semble variée. Une des perspectives de cette thèse est donc de poursuivre la caractérisation de cette réponse envers les espèces d’archées auxquelles les humains sont exposés au niveau des intestins et des bioaérosols. En plus de caractériser les cytokines et chimiokines produites lors d’une exposition à MBS et MSS, les études avec les modèles de souris permettraient de déterminer si MBS induit bel et bien une réponse immunitaire de type tolérogène. Par ailleurs, il serait intéressant d’étudier la réponse pulmonaire à d’autres espèces d’archées présentes dans l’air. Une étude effectuée par notre équipe a permis de démontrer que les archées étaient présentes dans l’air des poulaillers, en particulier l’espèce Methanobrevibacter woesei (Just et al., 2013). De façon intéressante, les travailleurs des poulaillers fortement contaminés aux archées rapportaient davantage de symptômes pulmonaires que ceux travaillant dans des poulaillers où les archées n’étaient pas ou peu présentes dans l’air (Just et al., 2013). Il serait alors pertinent d’étudier la réponse immune du modèle murin utilisé au chapitre IV lorsque les souris sont exposées à

M. woesei.

Puisque les archées sont retrouvées dans des bioaérosols complexes contenant une multitude d’agents biologiques divers, l’impact de ces microorganismes en combinaison avec d’autres agents importants des bioaérosols mérite d’être étudié. En effet, un modèle murin permettrait de déterminer les effets pulmonaires des archées combinées à d’autres contaminants des bioaérosols tels le SR, certains virus comme l’influenza, les endotoxines, le peptidoglycane et le β-D-glucan.

Afin de déterminer l’impact de MSS dans l’intestin des patients souffrant de MII, plusieurs stratégies pourraient être envisagées. Par exemple, il serait intéressant de déterminer l’endroit dans le système digestif humain où se situent les méthanogènes, et s’ils sont associés fortement ou pas à l’épithélium intestinal. Des transplantations fécales de sujets sains non porteurs de MSS à des patients atteints de MII dont les selles sont positives pour MSS pourraient aussi être envisagées (Aroniadis & Brandt, 2013). En effet, un suivi longitudinal de leur microflore intestinale et de leurs symptômes permettrait peut-être de savoir si la présence de MSS dans les intestins peut être réversible, et si sa disparition peut améliorer les

symptômes des patients. Enfin, un modèle murin mimant les pathologies des MII pourrait aussi être utilisé afin d’étudier si MSS a un rôle à jouer dans ces maladies (Valatas et al., 2013). Pour se faire, des gélules contenant des cellules de MBS ou de MSS vivantes pourraient être conçues et utilisées afin de coloniser le système digestif des souris.

Une perspective importante de cette thèse serait enfin de déterminer quelles sont les composantes inflammatoires de MSS et si ces dernières sont retrouvées à une fréquence moindre dans les cellules de MBS. Ces découvertes permettraient ainsi de comprendre les différences immunogéniques de MBS et de MSS. À titre d’exemple, la protéine membranaire Cpn II pourrait être une candidate potentielle vu ses propriétés immunomodulatrices (voir section 1.5.2 de l’introduction).

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