AUTHOR=Verma Arpana , Kaur Maninder , Luthra Princy , Singh Lakshyaveer , Aggarwal Divya , Verma Indu , Radotra Bishan D. , Bhadada Sanjay Kumar , Sharma Sadhna 

TITLE=Immunological aspects of host–pathogen crosstalk in the co-pathogenesis of diabetes and latent tuberculosis

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.957512

DOI=10.3389/fcimb.2022.957512

ISSN=2235-2988

ABSTRACT=<sec><title>Introduction</title><p>Diabetes is a potent risk factor for the activation of latent tuberculosis and worsens the tuberculosis (TB) treatment outcome. The major reason for mortality and morbidity in diabetic patients is due to their increased susceptibility to TB. Thus, the study was conducted to understand the crosstalk between <italic>M. tuberculosis</italic> and its host upon latent tuberculosis infection and under hyperglycemic conditions or diabetes.</p></sec><sec><title>Methods</title><p>An animal model was employed to study the relationship between latent tuberculosis and diabetes. BCG immunization was done in mice before infection with <italic>M. tuberculosis</italic>, and latency was confirmed by bacillary load, histopathological changes in the lungs and gene expression of <italic>hspX, tgs1, tgs3</italic> and <italic>tgs5</italic>. Diabetes was then induced by a single high dose of streptozotocin (150 mg/kg body weight). Host factors, like various cytokines and MMPs (Matrix metalloproteinases), which play an important role in the containment of mycobacterial infection were studied <italic>in vivo</italic> and <italic>in vitro</italic>.</p></sec><sec><title>Results</title><p>A murine model of latent TB was developed, which was confirmed by CFU counts (&lt;10<sup>4</sup> in the lungs and spleen) and granuloma formation in lungs in the latent TB group. Also, the gene expression of <italic>hspX, tgs1</italic>, and <italic>tgs5</italic> was upregulated, and after diabetes induction, blood glucose levels were &gt;200 mg/dl. An <italic>in vitro</italic> study employing a THP-1 macrophage model of latent and active tuberculosis under normal and high glucose conditions showed that dormant bacilli were better contained in the presence of 5.5 mM glucose concentration as compared with active bacilli. However, the killing and restriction efficiency of macrophages decreased, and CFU counts increased significantly with an increase in glucose concentration.</p></sec><sec><title>Discussion</title><p>The decreased levels of MCP-1, decreased expression of <italic>mmp-9</italic>, and increased expression of <italic>mmp-1</italic> in the latent group at high glucose concentrations could explain the failure of granuloma formation at high glucose conditions.</p></sec>