Document Type
Article
Publication Date
Spring 5-6-2021
Abstract
Previously, we found that pathological immune responses enhance the mortality rate of Mycobacterium tuberculosis (Mtb)-infected mice with type 2 diabetes mellitus (T2DM). In the current study, we evaluated the role of the cytokine IL-22 (known to play a protective role in bacterial infections) and type 3 innate lymphoid cells (ILC3s) in regulating inflammation and mortality in Mtb-infected T2DM mice. IL-22 levels were significantly lower in Mtb-infected T2DM mice than in nondiabetic Mtb-infected mice. Similarly, serum IL-22 levels were significantly lower in tuberculosis (TB) patients with T2DM than in TB patients without T2DM. ILC3s were an important source of IL-22 in mice infected with Mtb, and recombinant IL-22 treatment or adoptive transfer of ILC3s prolonged the survival of Mtb-infected T2DM mice. Recombinant IL-22 treatment reduced serum insulin levels and improved lipid metabolism. Recombinant IL-22 treatment or ILC3 transfer prevented neutrophil accumulation near alveoli, inhibited neutrophil elastase 2 (ELA2) production and prevented epithelial cell damage, identifying a novel mechanism for IL-22 and ILC3-mediated inhibition of inflammation in T2DM mice infected with an intracellular pathogen. Our findings suggest that the IL-22 pathway may be a novel target for therapeutic intervention in T2DM patients with active TB disease.
Persistant Identifier
http://hdl.handle.net/10950/4550
Publisher
PLOS PATHOGENS
Permanent Email Address
rama.vankayalapati@uthct.edu
Recommended Citation
Tripathi, Deepak; Radhakrishnan, Rajesh Kumar; Thandi, Ramya Sivangala; Paidipally, Padmaja; Devalraju, Kamakshi Prudhula; Kumar Neela, Venkata Sanjeev; McAllister, Madeline Kay; Samten, Buka; Lakshmi Valluri, Vijaya; and Vankayalapati, Ramakrishna, "IL-22 produced by type 3 innate lymphoid cells (ILC3s) reduces the mortality of type 2 diabetes mellitus (T2DM) mice infected with Mycobacterium tuberculosis" (2021). School of Medicine Faculty Publications and Presentations. Paper 12.
Description
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.