Abstract

Mycobacterium tuberculosis (Mtb) infects one-third of the world’s population and causes nearly 1.3 million deaths per year. Limited information is available about the immune responses during Mtb infection in type 2 diabetic hosts. Our laboratory developed an experimentally induced type 2 diabetes (T2DM) model in wild-type C57BL/6 mice and found that IL-22 and type 3 innate lymphoid cells (ILC3s) reduce inflammation and mortality of Mtb-infected T2DM mice. Our laboratory also found that Mtb-infected alveolar macrophages (AMs) from T2DM mice undergo necroptosis compared to Mtb-infected AMs of non-T2DM mice. In the current study, we determined whether recombinant IL-22 treatment of γMtb-stimulated macrophages of T2DM mice inhibits the expression of necroptosis, reduces inflammatory cytokine production, and regulates the metabolism of the macrophages. We found that γMtb stimulation of T2DM mice lung macrophages significantly enhanced the expression of necroptotic markers such as pMLKL (phosphorylated pseudokinase mixed lineage kinase domain-like protein) compared to γMtb-stimulated lung macrophages of non-diabetic mice. Recombinant IL-22 treatment significantly inhibited the expression of pMLKL by γMtb stimulated lung macrophages of T2DM mice. The treatment marginally reduced the glycolytic parameters of these macrophages. However, the treatment had no effect on pro-inflammatory cytokines (IL-6 and TNF-α) production by γMtb-stimulated macrophages of T2DM mice. In future studies, live Mtb H37Rv will be used to infect macrophages to determine cell viability and necroptosis. Further understanding of the mechanisms involved in IL-22-mediated inhibition of pMLKL will help to develop therapies to prevent excess inflammation in T2DM individuals with active and latent tuberculosis infection.

Date of publication

Spring 6-9-2023

Document Type

Thesis

Language

english

Persistent identifier

http://hdl.handle.net/10950/4230

Committee members

Ramakrishna Vankayalapati, Ph.D. (Thesis Advisor), Vijay Boggaram, Ph.D. (Committee Chair) and Buka Samten, M.D. (Committee Member)

Degree

Masters in Biotechnology

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