Higher Susceptibility of Type 1 Diabetic Rats to Mycobacterium tuberculosis Infection

Abstract

An association between diabetes mellitus and tuberculosis has been implicated for a long time. We have previously reported that Goto Kakizaki type 2 diabetic rats are highly susceptible to Mycobacterium (M.) tuberculosis infection. As a next step, we attempted to clarify whether type 1 diabetic rats are more susceptible to M. tuberculosis than non-diabetic wild-type (WT) rats. Here, we used the Komeda diabetes-prone (KDP) rat, as a model of type 1 diabetes mellitus. The infected KDP rats developed large granulomas without central necrosis in their lungs, liver or spleen. This was consistent with a significant increase in the number of colony-forming units (cfu) of M. tuberculosis in the lungs and spleen (p < 0.01). Insulin treatment resulted in significant reduction of tubercle bacilli in the infected KDP rats (p < 0.01). Pulmonary levels of interferon-γ, tumor necrosis factor-α and interleukin-1β mRNAs were higher in the infected diabetic rats than in WT rats. Alveolar macrophages from KDP rats were not fully activated by M. tuberculosis infection because the macrophages did not secrete nitric oxide (NO) that can kill M. tuberculosis (p < 0.01), but no significant difference in phagocytosis of tubercle bacilli by alveolar macrophages was observed between KDP and WT rats. Taken together, our findings indicate that type 1 diabetic rats are more susceptible to M. tuberculosis that WT rats.