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 nondiabetic 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. type 1 diabetic rat; type 1 diabetes mellitus; tuberculosis; cytokine.Tohoku

Aerosol Infection Model of Tuberculosis in Wistar Rats

“…However, the obvious limitation for drug screening remains the larger size, logistics and drug quantity requirements. In recent years, evidence is available where tuberculosis infected rats have necrotic lesions and chronic infections in the lungs [13, 14, 22], that are closer to the events observed in human disease than in the mice model. Thus, rats may provide an intermediate option in terms of representing more histopathological aspects of human disease than mice, yet not posing significantly higher demands on logistics and drug substance.…”

“…In recent years, several rat strains like Lewis, American cotton rats [12], and diabetic rat strains [13] have been successfully used to develop infection model of tuberculosis, particularly for investigating pathology and immune responses [14, 15]. However, there are no reports on therapy of tuberculosis in rat infection model.…”

Why does tuberculosis lead to specific inflammation?

“…KDP and WT rats. Taken together, it is appears that type 1 diabetic (KDP) and GK rats are more susceptible to M. tuberculosis that WT rats 15,16) .…”

Insulin Influences Autophagy Response Distinctively in Macrophages of Different Compartments

“…Experiments using Komeda diabetes-prone (KDP) rats infected with Mycobacterium tuberculosis (Mt), have shown that the burden of the bacilli observed in lungs and spleens of rats was more common when compared to healthy controls. In infected KDP rats, bacteremia impaired the production of nitric oxide (NO) by alveolar macrophages (AM) [8] that constitute an important entry barrier. Studies in alloxan-induced diabetic rats have also shown impairment in peripheral blood leukocyte phagocytic activities [9,10].…”