The role of macrophage-epithelial transition for mycobacterial granuloma progression and disease outcome

Santos, Débora Alexandra Costa dos

http://hdl.handle.net/10400.22/29555

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Authors

Santos, Débora Alexandra Costa dos

Advisor(s)

Resende, Mariana

Nova, Manuel Vila

Vieira, Mónica

Abstract(s)

Mucobacterial infections, primarily caused by Mycobacterium tuberculosis (Mtb) and Mycobacterium avium (M. avium) represent a global health problema. Following infection, bactéria are phagocytosed by macrophages, initiating na imune response that recruits additional imune cells to the site of infection, resulting in the formation of granulomas. Granulomas are organized structures consisting of a core of macrophages surrounded by B and T lymphocytes, that contain the bactéria. However, granulomas can envolve in ways that cause tissue damage and facilitate bacterial dissemination. Within these structures, macrophages undergo an epitelial transformation, acquiring epitelial-like properties suc as E-cadherin expression. The current study aims to elucidate the role of macrophage epithelization in shaping granuloma architecture, infection containment, and disease progression. To this end, we employed a mouse model with conditional disruption of E-cadherin expression in macrophages (Lyz2Cre x Cdh1fl/fl), wich was subsequently infected with either M. avium 2447 or M. avium 25291. Our initial objectives included analyzing the livers, spleens, and lungs to assess granuloma morphology, celular composition, E-cadherin expression, and bacterial growth. However animals did not become properly infected, altering the course of the project. Thus, we worked to understand the reasons behind the results obtained. It’s still nuclear why the animals do not develop the infection, but it become evidente that we cannot purpose with our initial aim using our Lyz2Cre x Cdh1fl/fl mouse colony. Nonetheless, it is important to refer that understanding the underlying mechanisms ofmacrophage epithelization remains crucial for identifying molecular targets to modulate granuloma Dynamics and develop therapeutic strategies for mycobacterial diseases.