Development of a diabetic mouse model of post tuberculosis lung disease 4520

Abstract Description Tuberculosis affects 10 million people and causes 1.3 million deaths each year. While Mycobacterium tuberculosis (Mtb) infections clear without causing apparent disease in most people, those with active tuberculosis disease can have residual lung damage that can lead to fibrosis. This lung damage has been described to be worse in type 2 diabetics. The disease process of post tuberculosis lung disease (PTLD) has not yet been fully characterized with one of the limitations being the lack of mouse model. We are establishing a mouse model to study the PTLD that occurs in both diabetic and non-diabetic mice. Our model induces type 2 diabetes mellitus using a combination of a high fat diet and streptozotocin in C3HeB/FeJ (C3H) mice. Continuous blood glucose monitoring demonstrates the development of diabetic state in 7 out of 9 animals that received HFD and STZ. Similar growth of Mtb was observed at 8 weeks post-infection in both diabetic and non-diabetic animals. Interestingly, diabetic C3H mice initially gained weight compared to non-diabetic controls prior to infection but progressively lost weight following treatment with antibacterial therapy of rifampicin, isoniazid, and pyrazinamide. Ongoing assessments are focused on characterizing the process of inflammation, fibrosis, and lung function in PTLD. Our preliminary results demonstrate potential for a mouse model that can be used to characterize the progression of PTLD in type 2 diabetes mellitus. Funding Sources Funding provided by Institute for Human Infections and Immunity and Center on Lung Disease, Inflammation, and Remodeling at University of Texas Medical Branch Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)