The Research Progress in Immunotherapy of Tuberculosis

Drug resistance in tuberculosis is a universal health problem, with India and China having the highest number of multidrug resistant tuberculosis (MDR-TB) cases globally. As cutaneous tuberculosis (CTB) accounts for 1.5% of all extrapulmonary tuberculosis, drug resistance in CTB remains less discussed and understood. The sensitivity and specificity of the routine diagnostic workup for CTB are low compared to pulmonary tuberculosis. Therefore, identifying drug resistance becomes challenging and needs a high index of suspicion. Molecular techniques such as polymerase chain reaction (PCR), line probe assays, DNA microarray, and sequencing help us to identify tubercular bacilli and drug resistance early. Prompt initiation of effective therapy reduces disease-related morbidity and mortality and makes the patient non-contagious. Lately, World Health Organization (WHO) has recommended using “all oral longer MDR TB regimen” for pulmonary and extrapulmonary drug-resistant TB instead of a painful older regimen requiring long term therapy with injectables. This review focuses on the drug resistance in CTB, various methods and newer techniques to diagnose them and recent updates on treatment guidelines.

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“…Table 3 enumerates the immunotherapeutic agents, most of which are under preclinical research. [ 48 ]…”

Section: Treatmentmentioning

confidence: 99%

Drug-resistance and its impact on cutaneous tuberculosis

Ramesh

Bhandari

Mahajan

2022

Indian Dermatol Online J

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“…In recent years, immunoadjuvant therapy for TB has made great progress. Some immunomodulators have entered clinical trials or been marketed, mainly including immunoactive substances, immunotherapeutic vaccines, chemical agents, 14 traditional Chinese medicine, and cell therapy 13 …”

Section: Introductionmentioning

confidence: 99%

“…Some immunomodulators have entered clinical trials or been marketed, mainly including immunoactive substances, immunotherapeutic vaccines, chemical agents, 14 traditional Chinese medicine, and cell therapy. 13 TB immunotherapeutic vaccine is used to regulate or selectively induce the potential of the immune system of MTB-infected people, to achieve the purpose of suppressing immune damage, recovering immune balance, improving immunity, and inhibiting or killing MTB in vivo. 15 It is mainly used to prevent individuals with latent tuberculosis infection from turning into active TB or help active TB patients recover faster.…”

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confidence: 99%

Mechanisms of ag85a/b DNA vaccine conferred immunotherapy and recovery from Mycobacterium tuberculosis‐induced injury

Wang,

Liang,

et al. 2023

Immunity Inflam & Disease

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Our previous research developed a novel tuberculosis (TB) DNA vaccine ag85a/b that showed a significant therapeutic effect on the mouse tuberculosis model by intramuscular injection (IM) and electroporation (EP). However, the action mechanisms between these two vaccine immunization methods remain unclear. In a previous study, 96 Mycobacterium tuberculosis (MTB) H37Rv‐infected BALB/c mice were treated with phosphate‐buffered saline, 10, 50, 100, and 200 μg ag85a/b DNA vaccine delivered by IM and EP three times at 2‐week intervals, respectively. In this study, peripheral blood mononuclear cells (PBMCs) from three mice in each group were isolated to extract total RNA. The gene expression profiles were analyzed using gene microarray technology to obtain differentially expressed (DE) genes. Finally, DE genes were validated by real‐time reverse transcription‐quantitive polymerase chain reaction and the GEO database. After MTB infection, most of the upregulated DE genes were related to the digestion and absorption of nutrients or neuroendocrine (such as Iapp, Scg2, Chga, Amy2a5), and most of the downregulated DE genes were related to cellular structural and functional proteins, especially the structure and function proteins of the alveolar epithelial cell (such as Sftpc, Sftpd, Pdpn). Most of the abnormally upregulated or downregulated DE genes in the TB model group were recovered in the 100 and 200 μg ag85a/b DNA IM groups and four DNA EP groups. The pancreatic secretion pathway downregulated and the Rap1 signal pathway upregulated had particularly significant changes during the immunotherapy of the ag85a/b DNA vaccine on the mouse TB model. The action targets and mechanisms of IM and EP are highly consistent. Tuberculosis infection causes rapid catabolism and slow anabolism in mice. For the first time, we found that the effective dose of the ag85a/b DNA vaccine immunized whether by IM or EP could significantly up‐regulate immune‐related pathways and recover the metabolic disorder and the injury caused by MTB.

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“…Recent estimates from a new World Health Organization report show that ~1/4 of the international population are infected with Mycobacterium tuberculosis ( M. tb ), which leads to 1.4 million deaths per year ( 3 , 4 ). Pathogenically, M. tb can survive for a long time in macrophages of tubercle granulomas in the human host ( 5 ). Macrophages are key components of the host innate immune responses to M. tb that could eliminate mycobacteria via different mechanisms, including apoptosis, immune-inflammatory responses and phagocytic activity ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Functions of exosomal non-coding RNAs to the infection with Mycobacterium tuberculosis

Wang

et al. 2023

Front. Immunol.

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Tuberculosis (TB) is a major infectious disease induced by Mycobacterium tuberculosis (M. tb) which causes the world’s dominant fatal bacterial contagious disease. Increasing studies have indicated that exosomes may be a novel option for the diagnosis and treatment of TB. Exosomes are nanovesicles (30-150 nm) containing lipids, proteins and non-coding RNAs (ncRNAs) released from various cells, and can transfer their cargos and communicate between cells. Furthermore, exosomal ncRNAs exhibit diagnosis potential in bacterial infections, including TB. Additionally, differential exosomal ncRNAs regulate the physiological and pathological functions of M. tb-infected cells and act as diagnostic markers for TB. This current review explored the potential biological roles and the diagnostic application prospects of exosomal ncRNAs, and included recent information on their pathogenic and therapeutic functions in TB.

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The Research Progress in Immunotherapy of Tuberculosis

Cited by 22 publications

References 128 publications

Drug-resistance and its impact on cutaneous tuberculosis

Drug-resistance and its impact on cutaneous tuberculosis

Mechanisms of ag85a/b DNA vaccine conferred immunotherapy and recovery from Mycobacterium tuberculosis‐induced injury

Functions of exosomal non-coding RNAs to the infection with Mycobacterium tuberculosis

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