IL-22 produced by type 3 innate lymphoid cells (ILC3s) reduces the mortality of type 2 diabetes mellitus (T2DM) mice infected with Mycobacterium tuberculosis
Authors: Padmaja Paidipally
Ramakrishna Vankayalapati
Buka Samten
Madeline Kay McAllister
Rajesh Kumar Radhakrishnan
Kamakshi Prudhula Devalraju
Ramya Sivangala Thandi
Deepak Tripathi
Venkata Sanjeev Kumar Neela
Vijaya Lakshmi Valluri
Journal: PLoS Pathogens (2019)
Discipline: MICROBIOLOGY
Keywords: immune responses; Mycobacterium tuberculosis; type 2 diabetes mellitus; IL-22; type 3 innate lymphoid cells
Affiliations: Department of Pulmonary Immunology, Center for Biomedical Research, The University of Texas Health Science Center, Tyler, Texas, TX, United States of America., Immunology and Molecular Biology Department, Bhagwan Mahavir Medical Research Centre, Hyderabad, Telangana, India.

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. 

Retracted: No

PubPeer comments:
 Supplemental Figure 7A. * Blue boxes: Two panels appear to show some data points. ![file] , 
 #1 Thank you very much for your comment. We will investigate and respond. , 
 #1 #1 Thank you for your comment. We looked at the raw data of this figure. It appeared that it is from two different samples. ![file] , 
 Thank you, Dr. Tripathi for posting these raw data. The quality of these graphs is low, though, lower than the published graphs. I cannot see the dots that I encircled in comment #1. Would it be possible to post them in higher resolution, please? , 
 Correction, May 2021 : https: journals.plos.org plospathogens article?id=10.1371 journal.ppat.1009578  Correction: * In Fig 6B, the boxes in 40X histology images are incorrectly positioned to correspond to the 100X images. Please see the correct Fig 6 below. * In S7A and S7B Fig, the incorrect representative flow cytometry images were used for the 5-month T2DM + Mtb group. Please see the correct S7 Fig below. The offending panel in Figure 7A has now been replaced by a new panel, without any explanation by the authors. Would they still be able to explain what happened here? ,