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- W4313368568 abstract "Abstract Diabetes is a significant risk factor for the development of active tuberculosis. In this study, we used mouse model of Streptozotocin/Nicotinamide (STZ/NA) induced non-obese type 2 diabetes mellitus (T2DM) to determine the effect of prior BCG vaccination on survival and immune responses to Mycobacterium tuberculosis (Mtb) infection. We found that at 6–7 months post-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 to Mtb-infected non-diabetic mice, however it reduced immunopathology of lung tissues. Further, we found increased survival of BCG vaccinated Mtb infected T2DM mice is associated with 2-fold expansion of IL-13 producing CXCR3+ T-regulatory cells as measured by flow cytometry, qRT-PCR and confocal microscopy. We also found that prior BCG vaccination restored the immunosuppressive function of T-regulatory cells of Mtb-infected T2DM mice and reduced inflammation. IL-13 producing T-regulatory cells of BCG vaccinated Mtb-infected T2DM mice converted proinflammatory M1 macrophages (iNOS) to anti-inflammatory M2 macrophage (Arg1) phenotype to suppress the inflammation. In contrast, anti-IL-13R antibody inhibited the conversion of macrophages from M1 to the M2 phenotype and enhanced the inflammatory cytokines (IL-6 and TNF-α) production. Our findings suggest a novel role for BCG in preventing excessive inflammation and mortality in T2DM mice infected with Mtb." @default.
- W4313368568 created "2023-01-06" @default.
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- W4313368568 date "2020-05-01" @default.
- W4313368568 modified "2023-09-23" @default.
- W4313368568 title "BCG vaccination reduces the mortality of <i>Mycobacterium tuberculosis</i>-infected type 2 diabetes mellitus (T2DM) mice through the induction of CXCR3+ T-regulatory cells" @default.
- W4313368568 doi "https://doi.org/10.4049/jimmunol.204.supp.85.11" @default.
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