Project description:C1q expression increases significantly in the peripheral blood of patients with active tuberculosis compared to healthy controls and individuals with latent TB infection. The percentage of C1q-expressing CD14 positive cells is significantly increased in active TB patients. C1q expression in the peripheral blood correlates with sputum smear positivity in tuberculosis patients and is reduced after anti-tuberculosis chemotherapy. Notably, receiver operating characteristic analysis showed that C1qC mRNA levels in peripheral blood efficiently discriminate active from latent tuberculosis infection and healthy controls. Additionally, C1qC protein level in pleural effusion shows improved power in discriminating tuberculosis from non-tuberculosis pleurisy when compared to other inflammatory markers, such as IL-6 and TNF-α C1q expression correlates with active disease in human tuberculosis. C1q could be a potential diagnostic marker to discriminate active tuberculosis from latent tuberculosis infection as well as tuberculosis pleurisy from non-tuberculosis pleurisy.
Project description:Individuals exposed to Mycobacterium tuberculosis (Mtb) may become infected and are classified as with latent tuberculosis infection (LTBI) and remain whole time life in this condition or develop active tuberculosis (TB). Among the multiple factors governing the outcome of the infection, dendritic cells (DC) play a major role in dictating protective immunity. However, current knowledge on the role of the diverse components of human DC in shaping specific T cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets along with the functional capability of monocyte-derived IFN-α DC to induce Mtb antigen-specific T cell response in patients with active TB, subjects with LTBI and healthy donors (HD). The percentage of BDCA3+ mDC2 and CD123+ pDC declined significantly in active TB patients with respect HD whereas the same subsets displayed a remarkable activation in LTBI. Simultaneously, IFN-α-driven differentiation of DC resulted profoundly impaired from monocytes of active TB patients as compared to LTBI and HD individuals. Importantly, the specific altered developmental trait of IFN-α DC from active TB patients was associated with a marked change of molecular signalings conveying antigen presentation as well as full inability to induce antigen-specific T cell response. Thus, these data unravel an unavoidable role of IFN-α in determining the induction of Mtb-specific protective immunity which is essential to control Mtb infection.
Project description:The aim of this study was to compare the transcriptional response to TB in regions of different incidence / prevalence. Experimental Design: Whole blood collected in tempus tubes from patients with different spectra of TB disease. All patients were sampled prior to the initiation of any antimycobacterial therapy. Active Pulmonary TB: PTB - All patients confirmed by isolation of Mycobacterium Tuberculosis on culture of sputum. Latent TB: LTB - All patients were screened at a tuberculosis clinic. All were positive by Interferon-Gamma Release assay(IGRA); specifically Quantiferon Gold In-Tube Assay (Cellestis, Australia). Latent patients had no clinical, or microbiological evidence of active infection and were asymptomatic. Experimental Variables: Patient group: Active PTB; Latent TB. There are no healthy controls in this dataset as it was being used for validation only. Controls: Latent TB individuals are used as a control for PTB in this dataset since there are few to no unexposed adult controls in Cape Town.
Project description:C1q expression increases significantly in the peripheral blood of patients with active tuberculosis compared to healthy controls and individuals with latent TB infection. The percentage of C1q-expressing CD14 positive cells is significantly increased in active TB patients. C1q expression in the peripheral blood correlates with sputum smear positivity in tuberculosis patients and is reduced after anti-tuberculosis chemotherapy. Notably, receiver operating characteristic analysis showed that C1qC mRNA levels in peripheral blood efficiently discriminate active from latent tuberculosis infection and healthy controls. Additionally, C1qC protein level in pleural effusion shows improved power in discriminating tuberculosis from non-tuberculosis pleurisy when compared to other inflammatory markers, such as IL-6 and TNF-α C1q expression correlates with active disease in human tuberculosis. C1q could be a potential diagnostic marker to discriminate active tuberculosis from latent tuberculosis infection as well as tuberculosis pleurisy from non-tuberculosis pleurisy. Complement gene expression in peripheral blood mononuclear cells of tuberculosis patients and controls were determined using whole genome transcriptional microarray assays. The mRNA and protein levels of three C1q components, C1qA, C1qB, and C1qC, were further validated by qRT-PCR and enzyme-linked immunosorbent assay, respectively. The percentages of C1q expression in CD14 positive cells were determined by flow cytometry. Finally, C1qC protein level was quantified in the pleural fluid of tuberculosis and non-tuberculosis pleurisy.
Project description:Tuberculosis (TB) is a serious infectious disease, but current methods of detection require improvement in sensitivity, efficiency or specificity. We conducted a microarray experiment, comparing the gene expression profiles in peripheral blood mononuclear cells among individuals with active TB, latent infection, and healthy conditions in a Taiwanese population. These differentially expressed genes may be potential biomarkers that can differentiate between active TB and latent infection. We isolated total RNA from the PBMC from 7 active TB, 7 latent infection, and 7 healthy individuals and profiled their transcriptional profiles to identify signficantly differentially expressed geens that differ among these three groups
Project description:Tuberculosis (TB) is responsible for the majority of mortality and morbidity associated with infectious diseases worldwide. The characterization of exact molecular components of immune response associated with protection against TB may help design more effective therapeutic interventions. In this study, we aimed to characterize the immune signature of memory T cells associated with active versus latent infection with Mycobacterium tuberculosis. Transcriptomic profiling using RNA sequencing was performed on memory CD4 T cells isolated from individuals with active TB (at diagnosis and 2 months post treatment), latent TB, as well as from TB negative healthy controls. Overall, we found specific gene signatures for each cohort that could successfully discriminate between individuals with active TB at diagnosis, treated active TB, latent TB and healthy controls.