IL-22 produced by type 3 innate lymphoid cells (ILC3s) reduces the mortality of type 2 diabetes mellitus (T2DM) mice infected with Mycobacterium tuberculosis

Autoři: Deepak Tripathi aff001;  Rajesh Kumar Radhakrishnan aff001;  Ramya Sivangala Thandi aff001;  Padmaja Paidipally aff001;  Kamakshi Prudhula Devalraju aff002;  Venkata Sanjeev Kumar Neela aff002;  Madeline Kay McAllister aff001;  Buka Samten aff001;  Vijaya Lakshmi Valluri aff002;  Ramakrishna Vankayalapati aff001
Působiště autorů: Department of Pulmonary Immunology, Center for Biomedical Research, The University of Texas Health Center, Tyler, Texas, TX, United States of America aff001;  Immunology and Molecular Biology Department, Bhagwan Mahavir Medical Research Centre, Hyderabad, Telangana, India aff002
Vyšlo v časopise: IL-22 produced by type 3 innate lymphoid cells (ILC3s) reduces the mortality of type 2 diabetes mellitus (T2DM) mice infected with Mycobacterium tuberculosis. PLoS Pathog 15(12): e1008140. doi:10.1371/journal.ppat.1008140
Kategorie: Research Article


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.

Klíčová slova:

Body weight – Epithelial cells – Flow cytometry – Inflammation – Tuberculosis – Adoptive transfer


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