Latent M. tuberculosis infection is associated with increased inflammatory cytokine and decreased suppressor of cytokine signalling (SOCS)-3 in the diabetic host

Authors

Kiran I. Masood, Aga Khan UniversityFollow
Muhammad Irfan, Aga Khan UniversityFollow
Qamar Masood, Aga Khan UniversityFollow
Maliha Yameen, Aga Khan UniversityFollow
Bushra Jamil, Aga Khan UniversityFollow
Nanik Ram, Aga Khan UniversityFollow
Shoaib Rao, Aga Khan UniversityFollow
Martin Rottenberg, Karolinska Institutet, Sweden
Zahra Hasan, Aga Khan UniversityFollow

Document Type

Article

Department

Pathology and Laboratory Medicine; Medicine; Diabetes/Endocrinology and Metabolism

Abstract

Tuberculosis (TB) outcomes are worsened by type II diabetes mellitus (DM). Protective immunity against Mycobacterium tuberculosis (MTB) is driven by cytokines. Latent TB (LTBi) is common but its effect on the diabetic host is not well understood. We investigated mycobacterial antigen-stimulated responses in peripheral blood mononuclear cell (PBMC) isolated from healthy endemic controls (EC), those with LTBi, DM groups with and without LTBi, as compared with TB patients. Cytokines were measured using a Luminex-based assay. Gene expression was determined by RT-PCR. In DM-LTBi cases, PPD-stimulated proinflammatory cytokines; IFN-γ, IL-6, IL-2, TNF-α and GM-CSF and anti-inflammatory cytokines, IL-5 and IL-13 were raised as compared with EC. DM-LTBi PPD-stimulated IFN-γ, IL-6 and TNF-α mRNA titres were found raised in DM-LTBi, whilst suppressor of cytokine signalling (SOCS)-3 expression was lowered. Within DM cases, stratification based on HbA1c levels revealed raised IFN-γ but lowered IL-6 gene expression in those with controlled levels as compared with uncontrolled glycaemic levels. Further, SOCS1 expression levels were found higher in DM cases with controlled glycaemia when compared with EC. Overall, we show that diabetics with LTBi manifest raised levels of inflammatory and anti-inflammatory cytokines concomitant with reduced SOCS3 mRNA expression. Reduced glycaemic control results in further inflammatory dysregulation impacting conversing impacting IFN-γ and IL-6 activation. These results suggest that dysregulated immune activation in diabetes is exacerbated by LTBi, lack of glycaemic control may further compromise immunity against MTB infection.

Comments

Pagination are not provided by the author/publisher.

Publication (Name of Journal)

Scandinavian Journal of Immunology

DOI

10.1111/sji.13134

Recommended Citation

Masood, K. I., Irfan, M., Masood, Q., Yameen, M., Jamil, B., Ram, N., Rao, S., Rottenberg, M., Hasan, Z. (2022). Latent M. tuberculosis infection is associated with increased inflammatory cytokine and decreased suppressor of cytokine signalling (SOCS)-3 in the diabetic host. Scandinavian Journal of Immunology, 95(4), e13134.
Available at: https://ecommons.aku.edu/pakistan_fhs_mc_pathol_microbiol/1540