Abstract
Diabetes is a significant risk factor for the development of active tuberculosis. In this study, we used a mouse model of type 2 diabetes mellitus (T2DM) to determine the effect of prior Bacillus Calmette-Guérin (BCG) vaccination on immune responses to Mycobacterium tuberculosis (Mtb) infection. We found that, at 6-7 months after Mtb infection, 90% of the Mtb-infected T2DM mice died, whereas only 50% of BCG-vaccinated T2DM-Mtb-infected mice died. Moreover, 40% of the PBS-treated uninfected T2DM mice and 30% of the uninfected BCG-vaccinated T2DM mice died, whereas all uninfected and infected nondiabetic mice survived. BCG vaccination was less effective in reducing the lung bacterial burden of Mtb-infected T2DM mice compared with Mtb-infected nondiabetic mice. BCG vaccination significantly reduced lung inflammation in Mtb-infected T2DM mice compared with that of unvaccinated T2DM mice infected with Mtb. Furthermore, reduced mortality of BCG-vaccinated Mtb-infected T2DM mice is associated with expansion of IL-13-producing CXCR3+ Tregs in the lungs of Mtb-infected T2DM mice. Recombinant IL-13 and Tregs from BCG-vaccinated Mtb-infected T2DM mice converted proinflammatory M1 macrophages to antiinflammatory M2 macrophages. Our findings suggest a potentially novel role for BCG in preventing excess inflammation and mortality in T2DM mice infected with Mtb.
Highlights
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a leading cause of death worldwide [1, 2]
Our findings demonstrate that Bacillus Calmette-Guérin (BCG) vaccination prevents the deaths of Mtb-infected Type 2 diabetes mellitus (T2DM) mice, and uninfected T2DM mice
We investigated whether BCG vaccination has any effect on immune responses to Mtb infection in T2DM mice
Summary
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a leading cause of death worldwide [1, 2]. Approximately 10% of LTBI+ individuals develop active disease during their lifetime [5, 6]. In 2017, it was estimated that 425 million of people worldwide were confirmed as diabetic or prediabetic [10], suggesting that it is important to understand the immune responses to Mtb in patients with diabetes. Type 2 diabetes mellitus (T2DM) patients with LTBI have a three-fold higher risk of developing active TB [2, 11, 12], and poor glycemic control is a major risk factor for developing active TB [13]. There is limited information available about the immune responses to Mtb in T2DM hosts [11, 15]
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