Challenges in TB research

Scriba, Thomas J.; Dinkele, Ryan; Warner, Digby F.; Mizrahi, Valerie

doi:10.1084/jem.20221334

Cited by 6 publications

(3 citation statements)

References 15 publications

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“… 5 2022 Tuberculosis prevalence: beyond the tip of the iceberg Novel stages and disease thresholds for TB Perspective Scriba et al. 54 2022 Challenges in TB research Challenges in developing new diagnostics and vaccines for TB control Perspective Yoon et al. 55 2022 CT and 18F-FDG PET abnormalities in contacts with recent tuberculosis infections but negative chest X-ray Systematic review of CT and PET-CT imaging of asymptomatic TB contacts with normal X-rays Systematic review Sossen et al.…”

Section: Resultsmentioning

confidence: 99%

Beyond latent and active tuberculosis: a scoping review of conceptual frameworks

Zaidi,

Coussens,

Seddon

et al. 2023

eClinicalMedicine

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Section: Resultsmentioning

confidence: 99%

Beyond latent and active tuberculosis: a scoping review of conceptual frameworks

Zaidi,

Coussens,

Seddon

et al. 2023

eClinicalMedicine

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“…When an individual is infected with Mtb, the actual infection dose may be much lower than the number of bacteria released by coughing because not all aerosols generated by the infected person are inhaled. In addition, it has been reported that symptomatic TB patients release Mtb aerosols not only by cough but also by exhalation, with an aerosol size of 0.5-5 μm, showing that actual infection can be achieved in the context of a sustained low-dose of bacteria ( 21 , 22 ). However, animal models for vaccine research in the preclinical stage can be established through a single, sufficient infection dose and used to evaluate vaccine efficacy.…”

Section: The Second Hurdle: a Gap Between Experiments And The Natural...mentioning

confidence: 99%

Bridging the gaps to overcome major hurdles in the development of next-generation tuberculosis vaccines

2023

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Although tuberculosis (TB) remains one of the leading causes of death from an infectious disease worldwide, the development of vaccines more effective than bacille Calmette-Guérin (BCG), the only licensed TB vaccine, has progressed slowly even in the context of the tremendous global impact of TB. Most vaccine candidates have been developed to strongly induce interferon-γ (IFN-γ)-producing T-helper type 1 (Th1) cell responses; however, accumulating evidence has suggested that other immune factors are required for optimal protection against Mycobacterium tuberculosis (Mtb) infection. In this review, we briefly describe the five hurdles that must be overcome to develop more effective TB vaccines, including those with various purposes and tested in recent promising clinical trials. In addition, we discuss the current knowledge gaps between preclinical experiments and clinical studies regarding peripheral versus tissue-specific immune responses, different underlying conditions of individuals, and newly emerging immune correlates of protection. Moreover, we propose how recently discovered TB risk or susceptibility factors can be better utilized as novel biomarkers for the evaluation of vaccine-induced protection to suggest more practical ways to develop advanced TB vaccines. Vaccines are the most effective tools for reducing mortality and morbidity from infectious diseases, and more advanced technologies and a greater understanding of host-pathogen interactions will provide feasibility and rationale for novel vaccine design and development.

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“…A deeper understanding of the disease's behavior and pathogenesis has uncovered more challenges for TB research toward elimination (14). An interesting and shocking observation from TB aerobiology studies was the occurrence of MTB transmission even with tidal breathing (15).…”

Section: Introductionmentioning

confidence: 99%

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

Sampath,

Moorthy,

Menon

et al. 2023

Front. Immunol.

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BackgroundMonocyte 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.MethodsWe sorted total monocytes including three subsets (HLA-DR+CD14+, HLA-DR+CD14+CD16+, and HLA-DR+CD16+cells) from peripheral blood mononuclear cells (PBMCs) of healthy and TB-infected individuals through flow cytometry and subjected them to NanoString-based miRNA profiling.ResultsThe outcome was the differential expression of 107 miRNAs particularly the downregulation of miRNAs in the active TB groups (both drug-resistant and drug-sensitive). The miRNA profile revealed differential expression signatures: i) decline of miR-548m in DR-TB alone, ii) decline of miR-486-3p in active TB but significant elevation only in LTB iii) elevation of miR-132-3p only in active TB (DR-TB and DS-TB) and iv) elevation of miR-150-5p in DR-TB alone. The directionality of functions mediated by monocyte miRNAs from Gene Set Enrichment Analysis (GSEA) facilitated two phenomenal findings: i) a bidirectional response between active disease (activation profile in DR-TB and DS-TB compared to LTB and HC) and latent infection (suppression profile in LTB vs HC) and ii) hyper immune activation in the DR-TB group compared to DS-TB.ConclusionThus, monocyte miRNA signatures provide pathological clues for altered monocyte function, drug resistance, and disease severity. Further studies on monocyte miRNAs may shed light on the immune regulatory mechanism for tuberculosis.

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Challenges in TB research

Abstract: Tuberculosis (TB) is an infectious disease bedeviled by complexity. This poses myriad challenges for a research ecosystem organized around specialist host- and/or pathogen-focused thrusts. Here, we highlight the key challenges and their implications for developing new tools to control TB.

Cited by 6 publications

References 15 publications

Beyond latent and active tuberculosis: a scoping review of conceptual frameworks

Beyond latent and active tuberculosis: a scoping review of conceptual frameworks

Bridging the gaps to overcome major hurdles in the development of next-generation tuberculosis vaccines

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

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