Low circulatory Fe and Se levels with a higher IL-6/IL-10 ratio provide nutritional immunity in tuberculosis

Kaushik, Sandeep Rai; Sahu, Sukanya; Guha, Hritusree; Saha, Sourav; Das, Ranjit; Kupa, Rukuwe-u; Kapfo, Wetetsho; Deka, Trinayan; Basumatary, Rumi; Thong, Asunu; Dasgupta, Angira; Goswami, Bidhan; Pandey, Amit; Saikia, Lahari; Khamo, Vinotsole; Das, Anjan Kumar; Nanda, Ranjan Kumar

doi:10.3389/fimmu.2022.985538

Cited by 3 publications

(1 citation statement)

References 34 publications

(41 reference statements)

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“…We further discuss different sample types, experimental platforms, and briefly the signaling pathways associated with the identified host-derived proteins. [12,13], [17], [29], [63] # , [66], [103][104][105][106][107][108][109][110][111][112][113][114] Mass spectrometry [22][23][24], [25] # , [115][116][117][118][119][120][121][122][123][124][125][126][127]] SOMAscan [19,20] Other [21], [70], [78], [128,129] Sputum/Saliva ELISA [7] Multiplex bead assay [14], [29] Mass spectrometry [26], [30], [31] # , [32]<...…”

Section: Introductionmentioning

confidence: 99%

From simple to complex: Protein‐based biomarker discovery in tuberculosis

Mousavian,

Källenius,

Sundling

2023

Eur J Immunol

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Tuberculosis (TB) is a deadly infectious disease that affects millions of people globally. TB proteomics signature discovery has been a rapidly growing area of research that aims to identify protein biomarkers for the early detection, diagnosis, and treatment monitoring of TB. In this review, we have highlighted recent advances in this field and how it is moving from the study of single proteins to high‐throughput profiling and from only using proteomics to include additional types of data in multi‐omics studies. We have further covered the different sample types and experimental technologies used in TB proteomics signature discovery, focusing on studies of HIV‐negative adults. The published signatures were defined as either coming from hypothesis‐based protein targeting or from unbiased discovery approaches. The methodological approaches influenced the type of proteins identified and were associated with the circulating protein abundance. However, both approaches largely identified proteins involved in similar biological pathways, including acute‐phase responses and T‐helper type 1 and type 17 responses. By analysing the frequency of proteins in the different signatures, we could also highlight potential robust biomarker candidates. Finally, we discuss the potential value of integration of multi‐omics data and the importance of control cohorts and signature validation.This article is protected by copyright. All rights reserved

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Section: Introductionmentioning

confidence: 99%

From simple to complex: Protein‐based biomarker discovery in tuberculosis

Mousavian,

Källenius,

Sundling

2023

Eur J Immunol

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Rv0495c regulates redox homeostasis in Mycobacterium tuberculosis

Pal,

Talwar,

Pandey

et al. 2024

Tuberculosis

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Hypothetical geneRv0495cregulates redox homeostasis inMycobacterium tuberculosis

Pal,

Talwar,

Pandey

et al. 2023

Preprint

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Mycobacterium tuberculosis(Mtb) has evolved sophisticated surveillance mechanisms to regulate and neutralize redox imbalances and associated lethal consequences. Failing this, the accumulated ROS induces toxicity by oxidizing a variety of biological molecules including proteins, nucleic acids and lipids. In the present study we identified Mtb’sRv0495cgene as an important regulator of oxidized cytosolic environment. Compared to wild type Mtb strain lackingthe Rv0495cgene, ΔRv0495c, had increased ROS and NAD+/NADH ratio creating a highly oxidized intracellular environment. ΔRv0495cstrain demonstrated slow growth phenotype underin vitroandex-vivogrowth conditions and demonstrated enhanced susceptibility to drugs, oxidative, nitrosative and hypoxic growth conditions. In addition, the increase in the superoxide radicals triggered a Fenton-like reaction rendering the ΔRv0495csusceptible to free iron. The increase in the intracellular ROS levels of the ΔRv0495cwas further corroborated by an increase in the expression of proteins involved in antioxidant defense and enhanced ROS-mediated oxidation and degradation of mycobacterial lipids. This superoxide-induced lipid degradation resulted in altered colony morphology and loss of membrane integrity in the ΔRv0495c. Surprisingly, despite showing a growth defect phenotype in anex-vivomacrophage infection model, the absence of theRv0495cgene in Mtb enhanced the pathogenicity and augmented the ability of the Mtb to grow inside the host. Gene expression analysis revealed a Rv0495c mediated immunomodulation of the host controls inflammation and helps creates a favorable niche for long-term survival of Mtb inside the host. In summary, the current study underscores the fact that the truce in the war between the host and the pathogen favors long-term disease persistence in tuberculosis. We believe targeting Rv0495c could potentially be explored as a strategy to potentiate the current anti-TB regimen.

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Low circulatory Fe and Se levels with a higher IL-6/IL-10 ratio provide nutritional immunity in tuberculosis

Cited by 3 publications

References 34 publications

From simple to complex: Protein‐based biomarker discovery in tuberculosis

From simple to complex: Protein‐based biomarker discovery in tuberculosis

Rv0495c regulates redox homeostasis in Mycobacterium tuberculosis

Hypothetical geneRv0495cregulates redox homeostasis inMycobacterium tuberculosis

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