MOUSE MODELS OF IMMUNODEFICIENCY

Despite the extensive employment of immunodeficient mouse models, their immune status is seldomly assessed by the research community, with possible unexpected and misleading results from the experiments. Furthermore, no standardized system for such assessment currently exists. This calls for the urge to have standardized and effective protocols to be applied periodically for the assessment and confirmation of the immune status in immunodeficient mouse models. On the other hand, new and more sophisticated immunodeficient mouse models are constantly being developed, necessitating continuing validation. The primary issue with immunodeficient people is their propensity for opportunistic infections, which is also present in the murine counterpart. This necessitates a complete assessment of the inflammatory responses of the mouse models to the same infections that afflict humans. In paper I, we developed and applied a standardized and reproducible multi-approach protocol that proved to be useful for the morpho-phenotypical assessment of immunodeficiency in 4 different immunodeficient mouse strains. The study also provided a comparison of the strengths and weaknesses of different laboratory methods for the identification and grading of immunodeficiency in the models. Our next step will be to extend the application of the protocol to other known murine immunodeficient models, as well as to immunodeficient mouse models of new development and those with possible unintended immune alterations. In paper II, we performed histology and immunohistochemistry/immunofluorescence on lung samples of mouse models of hyper-IgM syndrome infected with a clinically relevant opportunistic pathogen to confirm the efficacy of T-cell and hematopoietic stem cell gene editing for treating hyper-IgM syndrome. Our analysis contributed to the confirmation of the protective role of primed T-cells transfer and hematopoietic stem/progenitor cells in the infected mice, considered as surrogates of functional gene edited cells. In paper III, we performed a histological and immunohistochemical characterization of the pulmonary inflammatory response to an opportunistic pathogen of a mouse model of hyper-IgM syndrome. Our study identified certain odd pathways in the model's pulmonary inflammatory presentation that might be helpful in extrapolating to the human disease and offering fresh insights into the pathogenetic mechanisms of infection.

Grantor dc:publisher

Università degli Studi di Milano

Year dc:date

2023

Author dc:creator

• CAPPELLERI, ANDREA

Contributors dc:contributor

• tutor: E. Scanziani ; coordinatore: F. Ceciliani
• A. Cappelleri
• SCANZIANI, EUGENIO
• CECILIANI, FABRIZIO

• Settore VET/03 - Patologia Generale e Anatomia Patologica Veterinaria

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

http://dx.doi.org/10.13130/cappelleri-andrea_phd2023-06-09
10.13130/cappelleri-andrea_phd2023-06-09

OAI identifier oai:identifier

oai:air.unimi.it:2434/974348