Tuberculosis (TB), induced by the foxy Mycobacterium tuberculosis (Mtb), is still one of the top killers worldwide among infectious diseases. Although several antibiotics have been developed to significantly relieve the tuberculosis epidemics worldwide, there are still several important scientific challenges for tuberculosis. As one of the most critical issues for tuberculosis control, the accurate and timely diagnosis of tuberculosis is critical for the following therapy of tuberculosis and thus responsible for the effective control of drug-resistant tuberculosis. Current tuberculosis diagnostic methods in clinic are still facing the difficulties that they can’t provide the rapid diagnostic results with high sensitivity and accuracy, which therefore requires the development of more effective novel diagnostic strategies. In recent decades, nanomaterials have been proved to show promising potentials for novel nanobiosensor construction based on their outstanding physical, chemical and biological properties. Taking these promising advantages, nanomaterial-based biosensors show the potential to allow the rapid, sensitive and accurate tuberculosis diagnosis. Here, aiming to increase the development of more effective tuberculosis diagnostic strategy, we summarized the current progress of nanobiosensors for potential tuberculosis diagnosis application. We discussed the different kind diagnostic targets for tuberculosis diagnosis based on nanobiosensors, ranging from the detection of bacterial components from M. tuberculosis, such as DNA and proteins, to the host immunological responses, such as specific cytokine production, and to the direct whole cell detection of M. tuberculosis. We believe that this review would enhance our understandings of nanobiosensors for potential tuberculosis diagnosis, and further promote the future research on nanobiosensor-based tuberculosis diagnosis to benefit the more effective control of tuberculosis epidemic.
Background: Neonatal sepsis is an acute life-threatening condition in neonates, and a proper innate inflammatory is essential for prevention of the systemic inflammation associated with sepsis. As the most potential antigen-presenting innate immune cells, dentritic cells (DCs) dysfunction has been verified detrimental for sepsis. B and T lymphocyte attenuator (BTLA) is an immune-regulatory receptor shown to be associated with DCs dysfunction. However, the role of BTLA expression in myeloid DCs (mDCs) in neonatal sepsis is unknown. Methods: 61 of neonates with sepsis and 32 of neonates having no suspicion of sepsis as control were enrolled into this study. BTLA and HLA-DR expression in mDCs was measured by flow cytometry. To further study the role of BTLA in regulating mDCs function, BTLA+mDCs and BTLA-mDCs from septic neonates were sorted and utilized to evaluate the phagacytosis capacity, bactericidal ability as well as cytokine secretion of mDCs.Results: A higher percentage of BTLA+mDCs were observed in neonatal septic patients and the percentage was positively correlated to the duration of hospitalization of neonates as well as the severity of sepsis. Moreover, a decrease MFI expression of HLA-DR was found in mDCs in neonatal sepsis, which expression was negatively correlated with the percentage of BTLA+mDCs. When compared to BTLA-mDCs, sorted BTLA+mDCs exhibited lower FITC-dextran uptake capacity but more CFU E.coli number after cells challenged by E.coli. In addition, BTLA+mDCs comparatively secreted lower level of TNF-α and IL-12, but higher IL-10. Conclusions: A higher level of BTLA in mDCs in the observed septic neonates was associated to the severity of neonatal sepsis; therefore, BTLA expression in mDCs could be a useful biomarker help to determine the neonatal sepsis development. Additionally, BTLA negatively regulated the phagocytosis capacity and bactericidal ability of mDCs and lowered their antigen-presenting ability as well as altered cells into an anti-inflammatory phenotype. Thus, targeting BTLA in mDCs may be a new therapeutic strategy for neonatal sepsis.
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