Tuberculosis最新文献

Objective

Methods

Results

Conclusion

Tuberculosis is a global threat and is still a leading cause of death due to an infectious agent. The infection is spread through inhalation of M. tb containing aerosol droplets. Bacteria after reaching the lung alveoli are engulfed by alveolar macrophages, leading to an immune response. Then, pro-inflammatory cytokines are released by these macrophages, recruiting other antigen-presenting cells like dendritic cells. These cells phagocytose the bacteria and present mycobacterial antigens to naïve T cells. After activation by DCs, T cells differentiate into various T cells subsets, viz. CD4⁺, CD8⁺, Th17, Treg, Tfh cells and others display enormous diversification in their characteristics and functions. This review comprises a comprehensive literature on conventional and unconventional T cells, highlighting the polyfunctional T cells as well, their role in controlling TB infection, and their implications in the spectrum of TB infection. While some subsets such as CD4⁺ T cells are extensively studied, some T cell subsets such as gamma delta T cells and Tfh cells remain poorly understood in the pathophysiology of tuberculosis, despite having significant potential implications. The goal of TB eradication can be assisted by development of better vaccines against TB, which can effectively induce a robust and long-term T cells memory. The same has been discussed in the latter part of this review. BCG being the standalone commercialised TB vaccine so far has its limitations. Strategies for the enhancement of BCG along with novel studies in vaccine development, has also been discussed in great detail. Lastly, T cells display a complex interplay of an adaptive immune response against TB, with activation and enhancement of the innate immune responses. Therefore, it is critical to fully understand the role of various T cells subsets in pathophysiology of tuberculosis to provide better therapeutic inventions and improve patient care.

There is an increasingly urgent need to improve our ability to accurately forecast and control zoonotic diseases in wildlife reservoirs. We are confronted, however, with the continued challenge of accurately determining host infection status across space and time. This dilemma is epitomized with the Mycobacterium tuberculosis Complex (MTBC) pathogens and particularly in free-ranging wildlife, a critical global challenge for both human and animal health. In humans, transcriptional markers have been increasingly identified as a robust tool for diagnosing Mycobacterium tuberculosis (MTB) infection status but have rarely been utilized for diagnosing TB in free-ranging wildlife populations. Here, we report the first use of transcriptional markers to evaluate TB infection status in a free-ranging wildlife species, banded mongoose (Mungos mungo), infected with the MTBC pathogen, Mycobacterium mungi. In this study, we found that GBP5 and DUSP3 were significantly upregulated in free-ranging banded mongoose infected with M. mungi. These results provide the first step in developing an antemortem diagnostic tool for use in free-ranging wildlife species. Our results highlight the potential of transcriptional marker-based assays to advance our ability to detect and manage TB in free-ranging wildlife, especially in field studies and other scenarios when conventional diagnostics are not feasible.

Buryatia is a multidrug-resistant tuberculosis (MDR-TB) high-burden region in the Russian Far East with ethnically diverse population (30 % Mongoloid Buryats and 65 % Russians). Two hundred M. tuberculosis strains from newly-diagnosed patients were subjected to phenotypic testing and genotyping. The Beijing genotype was more prevalent among Russians than Buryats (68 % vs 53 %; P = 0.055). European non-Beijing genotypes (LAM, Ural, Haarlem) were double more prevalent in Buryats vs Russians (39.2 % vs 20.5 %; P = 0.01). Higher prevalence of Beijing among former prison inmates (79 % vs 61 % in other patients, P = 0.1) suggests its increased transmissibility. The Russian epidemic cluster B0/W148 was in 9.5 %, double smaller than elsewhere in Siberia. The hypervirulent Beijing 14717-15-cluster was endemic in Buryatia but paradoxically enough, it was more frequently isolated from Russians than Buryats (9.1 % vs 3.9 %; P = 0.2). Beijing subtypes B0/W148, CAO, and 14717-15 were associated with poly/multi-drug resistance (P = 0.01–0.0001). HIV coinfection was more frequent in Russians than in Buryats: 35/141 (24.8 %) vs 5/51 (9.8 %), P = 0.03. To conclude, M. tuberculosis population structure in Buryatia retained its singularities compared to other parts of Russia and remains strikingly different from the neighboring Mongolia. A circulation of strongly MDR-associated Beijing subtypes and drug-resistant non-Beijing strains highlights a risk of their broader dissemination.