IL-22 reduces the mortality of type 2 diabetes mellitus (T2DM) mice infected with Mycobacterium tuberculosis

Abstract IL-22 play an important role in protective immune responses against bacterial infections including Mtb and maintains homeostasis by regulating excess inflammation. IL-22 can also regulate glucose homeostasis, suggesting IL-22 pathway as a novel target for therapeutic intervention. Previously, we developed a mouse model of type 2 diabetes mellitus (T2DM) and found that pathological immune response enhances mortality of Mycobacterium tuberculosis (Mtb) infected T2DM mice. In the current study, we determined the role of IL-22 during Mtb infection in T2DM mice. We found innate lymphoid 3 cells (ILC3) are the major source for IL-22 and IL- 22 production was significantly reduced in the lungs and serum of T2DM mice infected with Mtb. Recombinant IL- 22 or adoptive transfer of ILC3 cells prolonged the survival of Mtb infected T2DM mice. Recombinant IL-22 prevented neutrophil accumulation near alveoli, reduced the serum insulin level and improved the lipid metabolism. Recombinant IL-22 also prevented neutrophil-mediated epithelial cell damage by inhibiting elastase production by neutrophils. Further, we found serum IL-22 levels were significantly less in tuberculosis (TB) patients with T2DM compared to TB patients without T2DM. Our findings suggest that IL-22 produced by ILC3 cells is essential to inhibit excess inflammation, epithelial cell damage in T2DM mice infected with Mtb.