Systemic and mucosal immune reactivity upon Mycobacterium avium ssp. paratuberculosis infection in mice
Arzu Koc1, Imke Bargen2, Abdulhadi Suwandi2
1Justus-Liebig-University Giessen, Department of Gastroenterology, Giessen, Germany.
Abstract:
Mycobacterium avium ssp. paratuberculosis (MAP) is the cause of Johne's disease, an inflammatory bowel disorder of ruminants. Due to the similar pathology, MAP was also suggested to cause Crohn's disease (CD). Despite of intensive research, this question is still not settled, possibly due to the lack of versatile mouse models. The aim of this study was to identify basic immunologic mechanisms in response to MAP infection. Immune compromised C57BL/6 Rag2-/- mice were infected with MAP intraperitoneally. Such chronically infected mice were then reconstituted with CD4+ and CD8+ T cells 28 days after infection. A systemic inflammatory response, detected as enlargement of the spleen and granuloma formation in the liver, was observed in mice infected and reconstituted with CD4+ T cells. Whereby inflammation in infected and CD4+CD45RB(hi) T cell reconstituted animals was always higher than in the other groups. Reconstitution of infected animals with CD8+ T cells did not result in any inflammatory signs. Interestingly, various markers of inflammation were strongly up-regulated in the colon of infected mice reconstituted with CD4+CD45RB(lo/int) T cells. We propose, the usual non-colitogenic CD4+CD45RB(lo/int) T cells were converted into inflammatory T cells by the interaction with MAP. However, the power of such cells might be not sufficient for a fully established inflammatory response in the colon. Nevertheless, our model system appears to mirror aspects of an inflammatory bowel disease (IBD) like CD and Johne's diseases. Thus, it will provide an experimental platform on which further knowledge on IBD and the involvement of MAP in the induction of CD could be acquired.
Insights
Mycobacterium avium ssp. paratuberculosis (MAP) infection in mice showed that CD4+ T cells induced inflammation, potentially mirroring inflammatory bowel disease (IBD) and Crohn's disease (CD). This model aids IBD research.
Area of Science:
- Immunology
- Microbiology
- Gastroenterology
Background:
- Mycobacterium avium ssp. paratuberculosis (MAP) causes Johne's disease, an inflammatory bowel disorder in ruminants.
- MAP's potential role in Crohn's disease (CD), a human inflammatory bowel disease (IBD), remains unclear due to limited animal models.
- Understanding immune responses to MAP is crucial for elucidating IBD pathogenesis.
Purpose of the Study:
- To investigate the immunologic mechanisms underlying MAP infection.
- To establish a versatile mouse model for studying MAP-induced inflammation relevant to IBD and CD.
- To explore the role of T cell subsets in the host response to MAP.
Main Methods:
- Immune-compromised C57BL/6 Rag2-/- mice were infected with MAP.
- Mice were reconstituted with CD4+ or CD8+ T cells 28 days post-infection.
- Inflammatory responses were assessed by spleen size, liver granuloma formation, and colonic inflammation markers.
Main Results:
- Mice reconstituted with CD4+ T cells, particularly CD4+CD45RB(hi), exhibited systemic inflammation (enlarged spleen, liver granulomas).
- CD8+ T cell reconstitution did not induce significant inflammatory signs.
- Mice receiving CD4+CD45RB(lo/int) T cells showed increased colonic inflammation markers, suggesting MAP-induced conversion of non-colitogenic T cells.
Conclusions:
- The developed mouse model mimics aspects of IBD, Johne's disease, and potentially CD.
- MAP infection can induce inflammatory responses mediated by specific CD4+ T cell subsets.
- This model provides a platform for further research into IBD pathogenesis and MAP's role in Crohn's disease.
