Krishnananthasivam, Shivankari, Sathkumara, Harindra Dharshan, Corea, Enoka, Natesan, Mohan, and De Silva, Aruna Dharshan (2017) Gene Expression Profile of Human Cytokines in Response to Burkholderia pseudomallei Infection. mSphere, 2 (2). e00121-17.

Preview

PDF (Published Version) - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview

Abstract

Melioidosis is an underreported infectious disease, caused by the Gram-negative bacterium Burkholderia pseudomallei. Understanding the disease susceptibility and pathogenesis is crucial for developing newer diagnostic and therapeutic strategies for this life-threatening infection. In this study, we aimed to analyze the gene expression levels of important cytokines in melioidosis patients and establish useful correlates with disease biomarkers compared to cases of sepsis infection caused by other pathogens and healthy individuals. A Qiagen common human cytokines array profiling the gene expression of 84 important cytokines by real-time quantitative PCR (RT-qPCR) was used. We analyzed 26 melioidosis cases, 5 healthy controls, and 10 cases of sepsis infection caused by other pathogens. Our results showed consistently upregulated expression of interleukins (IL) interleukin-4 (IL-4), interleukin-17 alpha (IL-17A), IL-23A, and IL-24, interferons (IFN) interferon alpha 1 (IFNA1) and interferon beta 1 (IFNB1), tumor necrosis factor (TNF) superfamily 4 (TNFSF4), transforming growth factor (TGF) superfamily, bone morphogenetic proteins 3 and 6 (BMP3 and BMP6), transforming growth factor beta 1 (TGFB1), and other growth factors, including macrophage colony-stimulating factor (M-CSF), C-fos-induced growth factor (FIGF), and platelet-derived growth factor alpha (PDGFA) polypeptide, in melioidosis patients compared to their expression in other sepsis cases, irrespective of comorbidities, duration of fever/clinical symptoms, and antibiotic treatment. Our findings indicate a dominant Th2- and Th17-type-cytokine response, suggesting that their dysregulation at initial stages of infection may play an important role in disease pathogenesis. IL-1A, interleukin-1 beta (IL-1B), and IL-8 were significantly downregulated in septicemic melioidosis patients compared to their expression in other sepsis cases. These differentially expressed genes may serve as biomarkers for melioidosis diagnosis and targets for therapeutic intervention and may help us understand immune response mechanisms.

Item ID:	77466
Item Type:	Article (Research - C1)
ISSN:	2379-5042
Copyright Information:	Copyright © 2017 Krishnananthasivam et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Date Deposited:	08 Feb 2023 03:50
FoR Codes:	31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310702 Infectious agents @ 100%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions @ 100%
Downloads:	Total: 62 Last 12 Months: 5
	More Statistics