Influence of Genetic Polymorphism Towards Pulmonary Tuberculosis Susceptibility

Tuberculosis (TB) is still remains the major threat for human health worldwide. Several case-control, candidate-gene, family studies and genome-wide association studies (GWAS) suggested the association of host genetic factors to TB susceptibility or resistance in various ethnic populations. Moreover, these factors modulate the host immune responses to tuberculosis. Studies have reported genetic markers to predict TB development in human leukocyte antigen (HLA) and non-HLA genes like killer immunoglobulin-like receptor (KIR), toll-like receptors (TLRs), cytokine/chemokines and their receptors, vitamin D receptor (VDR) and SLC11A1 etc. Highly polymorphic HLA loci may influence antigen presentation specificities by modifying peptide binding motifs. The recent meta-analysis studies revealed the association of several HLA alleles in particular class II HLA-DRB1 with TB susceptibility and valuable marker for disease development especially in Asian populations. Case-control studies have found the association of HLA-DR2 in some populations, but not in other populations, this could be due to an ethnic specific association of gene variants. Recently, GWAS conducted in case-control and family based studies in Russia, Chinese Han, Morocco, Uganda and Tanzania revealed the association of genes such as ASAP1, Alkylglycerol monooxygenase (AGMO), Forkhead BoxP1 (FOXP1), C-terminal domain phosphatase 1 (UBLCP1) and intergenic SNP rs932347C/T with TB. Whereas, SNP rs10956514A/G were not associated with TB in western Chinese Han and Tibetan population. In this review, we summarize the recent findings of genetic variants with susceptibility/resistance to TB

Monocyte and Macrophage miRNA: Potent Biomarker and Target for Host-Directed Therapy for Tuberculosis

The end TB strategy reinforces the essentiality of readily accessible biomarkers for early tuberculosis diagnosis. Exploration of microRNA (miRNA) and pathway analysis opens an avenue for the discovery of possible therapeutic targets. miRNA is a small, non-coding oligonucleotide characterized by the mechanism of gene regulation, transcription, and immunomodulation. Studies on miRNA define their importance as an immune marker for active disease progression and as an immunomodulator for innate mechanisms, such as apoptosis and autophagy. Monocyte research is highly advancing toward TB pathogenesis and biomarker efficiency because of its innate and adaptive response connectivity. The combination of monocytes/macrophages and their relative miRNA expression furnish newer insight on the unresolved mechanism for Mycobacterium survival, exploitation of host defense, latent infection, and disease resistance. This review deals with miRNA from monocytes, their relative expression in different disease stages of TB, multiple gene regulating mechanisms in shaping immunity against tuberculosis, and their functionality as biomarker and host-mediated therapeutics. Future collaborative efforts involving multidisciplinary approach in various ethnic population with multiple factors (age, gender, mycobacterial strain, disease stage, other chronic lung infections, and inflammatory disease criteria) on these short miRNAs from body fluids and cells could predict the valuable miRNA biosignature network as a potent tool for biomarkers and host-directed therapy

A comparative study on chitosan nanoparticle synthesis methodologies for application in aquaculture through toxicity studies

Abstract Chitosan nanoparticles (CSNPs) have been recently used for various applications in aquaculture, especially as drug carriers. The aim of this study was to synthesise and investigate a superlative method of CSNP synthesis for application in aquaculture through aquaculture‐based toxicology screening methods. Two different methods were analysed: the first a direct ionic gelation method (A) and the other involving a low‐molecular‐weight chitosan microparticle intermediate method (B). Dynamic light scattering characterisation revealed that the CSNP particle sizes were 192.7 ± 11.8 and 22.9 nm from methods A and B, respectively. The LC50 values for brine shrimp toxicity were found to be 1.51 and 0.02 ppt in 24 h for methods A and B, respectively. Acute toxicity studies in Litopenaeus vannamei rendered LC50 values of 3235.94 and 2884.03 ppt in 24 h for methods A and B, respectively. Zebrafish toxicity studies revealed mortality rates of 21.67% and 55% at 20 mg/L concentration for methods A and B, respectively, with an increased expression of intracellular reactive oxygen species in method B. From these findings, it can be concluded that a comparatively reduced toxicity of CSNPs derived from ionic gelation method makes it more appropriate for application in aquaculture

Plasma Vitamin D levels in correlation with circulatory proteins could be a potential biomarker tool for pulmonary tuberculosis and treatment monitoring

Background: Tuberculosis (TB), a life-threatening immune challenging disease to the global human community has to be diagnosed earlier and eliminated in the upcoming era. Vitamin D, a fat-soluble micronutrient, mainly from epidermal cells of the skin and a few dietary sources, is associated with the immune system in various disease management. Therefore, a better understanding of vitamin D metabolism and immune function in tuberculosis should be studied for the consideration of biomarkers. Methods: The study consist of Pulmonary Tuberculosis (PTB) patients (n = 32) at two-time points: Baseline (PTB BL) and after 6 months of anti-TB treatment (ATT) (PTB PT), latently Mtb infected (IFNγ + ) group (n = 32) and a non-LTB healthy control (IFNγ-) group (n = 32). Vitamin D levels were measured using High-performance liquid chromatography (HPLC). The cytokine data from the same participants assayed by ELISA from our earlier in�vestigations were used to correlate it with serum Vitamin D levels. Results: The assayed serum Vitamin D levels between the groups showed significantly lowered levels in PTB BL when compared with IFNγ + and IFNγ- groups. And, the Vitamin D levels in the PTB group after ATT were significantly lower than the baseline levels. The Vitamin D data were compared with pro- and anti-inflammatory cytokines and adipokines levels by performing a principal component regression analysis. Based on the PC scores, the study group showed distinct clusters for the TB group and control group. And, the correlation analysis be�tween the study group and immunological indices showed significant correlations. Vitamin D significantly correlated with IFNγ, TNFα, IL17A, IL-4 and Resistin in the TB group, whereas IL-6 and G-CSF in the control group. Conclusion: The baseline measurement of Vitamin D levels was significantly decreased in the PTB group when compared with IFNγ + and IFNγ- groups showing the importance of Vitamin D as a preventive factor against the TB disease progression. The six-month post-treatment of TB showed a further decrease in Vitamin D levels in PTB. The significantly correlated immunological indices with Vitamin D levels are the biomarker profile that could predict TB

Downregulation of monocyte miRNAs: implications for immune dysfunction and disease severity in drug-resistant tuberculosis

Monocyte miRNAs govern both protective and pathological responses during tuberculosis (TB) through their differential expression and emerged as potent targets for biomarker discovery and host-directed therapeutics. Thus, this study examined the miRNA profile of sorted monocytes across the TB disease spectrum [drug-resistant TB (DR-TB), drug-sensitive TB (DS-TB), and latent TB] and in healthy individuals (HC) to understand the underlying pathophysiology and their regulatory mechanism

Plasma chemokines CXCL10 and CXCL9 as potential diagnostic markers of drug-sensitive and drug-resistant tuberculosis

Tuberculosis (TB) diagnosis still remains to be a challenge with the currently used immune based diagnostic methods particularly Interferon Gamma Release Assay due to the sensitivity issues and their inability in differentiating stages of TB infection. Immune markers are valuable sources for understanding disease biology and are easily accessible. Chemokines, the stimulant, and the shaper of host immune responses are the vital hub for disease mediated dysregulation and their varied levels in TB disease are considered as an important marker to define the disease status. Hence, we wanted to examine the levels of chemokines among the individuals with drug-resistant, drug-sensitive, and latent TB compared to healthy individuals. Our results demonstrated that the differential levels of chemokines between the study groups and revealed that CXCL10 and CXCL9 as potential markers of drug-resistant and drug-sensitive TB with better stage discriminating abilities