Development of a Nomogram Based on Transcriptional Signatures, IFN-γ Response and Neutrophils for Diagnosis of Tuberculosis.

Purpose: Tuberculosis (TB) is a major global health threat and its diagnosis remains challenging. This study aimed to develop a nomogram that incorporated peripheral blood transcriptional signatures and other blood tests for the diagnosis of tuberculosis.

Patients And Methods: Patients with TB, patients with other definite pulmonary diseases (OPD), individuals with latent tuberculosis infection (LTBI), and healthy controls (HC) were retrospectively enrolled between May 2017 and April 2018.

Disseminated tuberculosis is associated with impaired T cell immunity mediated by non-canonical NF-κB pathway.

Objectives: The mechanism that leads to disseminated tuberculosis in HIV-negative patients is still largely unknown. T cell subsets and signaling pathways that were associated with disseminated tuberculosis were investigated.

Methods: Single-cell profiling of whole T cells was performed to identify T cell subsets and enriched signaling pathways that were associated with disseminated tuberculosis.

Identification of ferroptosis-related gene signature for tuberculosis diagnosis and therapy efficacy.

Diagnosis of tuberculosis remains a challenge when microbiological tests are negative. Immune cell atlas of patients with tuberculosis and healthy controls were established by single-cell transcriptome. Through integrated analysis of scRNA-seq with microarray and bulk RNA sequencing data, a ferroptosis-related gene signature containing ACSL4, CTSB, and TLR4 genes that were associated with tuberculosis disease was identified.

Single-cell profiling identifies T cell subsets associated with control of tuberculosis dissemination.

To identify T cell subsets associated with control of tuberculosis, single-cell transcriptome and T cell receptor sequencing were performed on total T cells from patients with tuberculosis and healthy controls. Fourteen distinct subsets of T cells were identified by unbiased UMAP clustering. A GZMK-expressing CD8 cytotoxic T cell cluster and a SOX4-expressing CD4 central memory T cell cluster were depleted, while a MKI67-expressing proliferating CD3 T cell cluster was expanded in patients with tuberculosis compared with healthy controls.

Evaluation of IFIT3 and ORM1 as Biomarkers for Discriminating Active Tuberculosis from Latent Infection.

Objective: Current commercially available immunological tests cannot be used for discriminating active tuberculosis (TB) from latent TB infection. To evaluate the value of biomarker candidates in the diagnosis of active TB, this study aimed to identify differentially expressed genes in peripheral blood mononuclear cells (PBMCs) between patients with active TB and individuals with latent TB infection by transcriptome sequencing.

Methods: The differentially expressed genes in unstimulated PBMCs and in Mycobacterium tuberculosis (Mtb) antigen-stimulated PBMCs from patients with active TB and individuals with latent TB infection were identified by transcriptome sequencing.

[Expression of CD160 in natural killer (NK) cells from patients with active tuberculosis and its relationship with cell functions].

Objective To investigate the relationship between the CD160 expression and anti-tuberculosis immunity. Methods Fluorescence quantitative real-time PCR was used to detect the expression of CD160 in peripheral blood mononuclear cells (PBMCs). Flow cytometry was used to analyze the expression of CD160 on main subtypes of PBMCs, such as T cells, B cells, NK cells and monocytes.

Tim-3 expression is induced by mycobacterial antigens and identifies tissue-resident subsets of MAIT cells from patients with tuberculosis.

Tissue-resident MAIT cells in tuberculous pleural effusions, the site of tuberculosis infection, were investigated in the study. Tim-3CD69CD103 and CD39CD69CD103 tissue-resident MAIT cell subsets were identified in tuberculous pleural effusions. Tim-3 expression in MAIT cells was greatly induced and CD39 expression was elevated following ex vivo stimulation with Mycobacterium tuberculosis antigens.

Mesenchymal-epithelial Transition Factor Regulates Monocyte Function during Mycobacterial Infection via Indoleamine 2,3-dioxygenase.

Objective: Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), causes an estimated 1.6 million human deaths annually, but the pathogenesis of TB remains unclear. Immunity plays a critical role in the onset and outcome of TB.

Chronic psychological stress impairs germinal center response by repressing miR-155.

Germinal centers (GC) are vital to adaptive immunity. BCL6 and miR-155 are implicated in control of GC reaction and lymphomagenesis. FBXO11 causes BCL6 degradation through ubiquitination in B-cell lymphomas.

[The expression of T-bet is negatively correlated with the expressions of IFN-γ and TNF-α in CD4 T cells of patients with active pulmonary tuberculosis].

Objective To investigate the relationship between T box expressed in T cells (T-bet) and the production of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and interleukin 2 (IL-2) in CD4T cells of patients with active pulmonary tuberculosis. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood by density gradient centrifugation. Individuals with latent Mycobacterium tuberculosis (MTB) infection were screened by enzyme-linked immunospot assay (ELISPOT).

Enhanced immune response of MAIT cells in tuberculous pleural effusions depends on cytokine signaling.

The functions of MAIT cells at the site of Mycobacterium tuberculosis infection in humans are still largely unknown. In this study, the phenotypes and immune response of MAIT cells from tuberculous pleural effusions and peripheral blood were investigated. MAIT cells in tuberculous pleural effusions had greatly enhanced IFN-γ, IL-17F and granzyme B response compared with those in peripheral blood.

Mucosal-associated invariant T cells from patients with tuberculosis exhibit impaired immune response.

Objectives: To identify factors which regulate MAIT cell response to Mycobacterium tuberculosis antigens, and to investigate the role of MAIT cells in patients with active tuberculosis.

Methods: Immune response of MAIT cells to M. tuberculosis antigens were compared between patients with active TB and healthy controls by flow cytometry and RNA sequencing.

Elevated expression of T-bet in mycobacterial antigen-specific CD4(+) T cells from patients with tuberculosis.

T-bet is a T-box transcriptional factor that controls the differentiation and effector functions of CD4 T cells. In this study, we studied the role of T-bet in regulating CD4(+) T cell immunity against tuberculosis (TB). T-bet expression in Mycobacterium tuberculosis antigen-specific CD4(+) T cells was significantly higher in patients with active TB than in individuals with latent TB infection (p<0.

miR-223 is upregulated in monocytes from patients with tuberculosis and regulates function of monocyte-derived macrophages.

Tuberculosis (TB) is a serious infectious disease that most commonly affects the lungs. Macrophages are among the first line defenders against establishment of Mycobacterium tuberculosis infection in the lungs. In this study, we found that activation and cytokine production in monocyte-derived macrophages (MDM) from patients with active TB was impaired.

[Down-regulated expression of c-Jun in peripheral blood mononuclear cells of patients with severe secondary pulmonary tuberculosis].

Objective: To compare the expression of c-Jun in severe versus mild secondary pulmonary tuberculosis (TB) and understand the relationship of the c-Jun expression with the inflammation and immune injury of severe secondary TB patients.

Methods: Differentially expressed genes were screened in patients with severe TB, the ones with mild TB and healthy controls using Affymetrix human gene expression chips. Bioinformatic analysis was performed on the results of the gene chip screening.

[Gene expression profiling and verification for severe secondary pulmonary tuberculosis patients].

Objective: To explore the gene expression profiles of severe secondary pulmonary tuberculosis patients.

Methods: From May 2012 to October 2013, a total of 103 eligible patients with secondary pulmonary tuberculosis were recruited from Institution of Tuberculosis Research of PLA Hospital No. 309.

Mucosal-associated invariant T-cell function is modulated by programmed death-1 signaling in patients with active tuberculosis.

Rationale: Mucosal-associated invariant T (MAIT) cells have been proven to play an important role in host defense against mycobacterial infection in animal infection models; however, the functional role of MAIT cells in patients with active tuberculosis (TB) is still largely unknown.

Objectives: To understand the clinical features and functions of MAIT cells in patients with active TB.

Methods: MAIT cells were analyzed in patients with pulmonary TB, tuberculous pleurisy, and tuberculous peritonitis by flow cytometry.

Increased frequency of ILT2-expressing CD56(dim)CD16(+) NK cells correlates with disease severity of pulmonary tuberculosis.

The functional role of ILT2 in anti-tuberculosis immunity remains to be elucidated. In this study, we investigated expression and functions of ILT2 on NK cells during TB infection. The frequency of CD56(dim)CD16(+) NK cells that expressed ILT2 was significantly elevated in patients with active pulmonary TB as compared with tuberculin-positive healthy controls (p < 0.

Identification of CD244-expressing myeloid-derived suppressor cells in patients with active tuberculosis.

Development of active TB is accompanied by immune suppression and the underlining mechanisms have been explored extensively in recent years. MDSCs are a heterogeneous group of immature and progenitor myeloid cells with strong immunosuppressive ability for both natural and adaptive immunity. In our analysis of CD244 (2B4)-expressing cells in PBMCs from patients with active TB, a CD3(-)CD244(high) subpopulation was identified.

Involvement of CD244 in regulating CD4+ T cell immunity in patients with active tuberculosis.

CD244 (2B4) is a member of the signaling lymphocyte activation molecule (SLAM) family of immune cell receptors and it plays an important role in modulating NK cell and CD8(+) T cell immunity. In this study, we investigated the expression and function of CD244/2B4 on CD4(+) T cells from active TB patients and latent infection individuals. Active TB patients had significantly elevated CD244/2B4 expression on M.

Diagnostic performance of multiplex cytokine and chemokine assay for tuberculosis.

Simultaneous detection of multiple biomarkers might lead to improved diagnostic performance for Mycobacterium tuberculosis infection. In this study, we screened soluble biomarkers that had significant differences in patients with active tuberculosis and healthy controls and evaluated the diagnostic performance of the multiplex cytokine/chemokine assay. Overall, 178 patients with active pulmonary tuberculosis, 156 healthy individuals and 35 patients with bacterial pneumonia or lung cancer were evaluated.

[Prepared the monoclonal antibody associated with hepatocellular carcinoma and analyzed its epitope].

Aim: To prepare the monoclonal antibodies associated with hepatocellular carcinoma (HCC) for diagnosis.

Methods: 3 BALB/c mice were immunized with high metastasis characteristic HCC cells (HCCLM-6). The splenocytes from the immunized mice were fused with murine myeloma cells (Sp2/0).

Modulation of T cell cytokine production by miR-144* with elevated expression in patients with pulmonary tuberculosis.

microRNAs have a critical role in regulating innate and adaptive immunity. To understand whether microRNAs play roles in regulating immune responses to Mycobacterium tuberculosis infection in humans, microRNA expression profiling was performed in PBMCs from pulmonary tuberculosis patients and healthy controls. Analysis of expression profiles showed that expression of 30 microRNAs was significantly altered during active TB as compared with healthy controls, 28 microRNAs were up-regulated and 2 microRNAs down-regulated.

Recombinant heat shock protein 65 carrying hepatitis B core antigen induces HBcAg-specific CTL response.

Many studies have provided evidence that heat shock protein 65 (Hsp65) can elicit potent specific cellular adaptive immune responses (e.g. CD8(+) cytotoxic T-cell effectors or classic CTLs) based on their ability to chaperone antigenic peptides.

Construction and evaluation of anti-gastrin immunogen based on P64K protein.

Aim: To construct two kinds of anti-gastrin immunogen based on P64K protein from Neisseria meningitids and to compare their immunogenic effect.

Methods: G17P64K gene was cloned and ligated into pET28a plasmid, then transformed into BL21(DE3). After inoculation of LB medium and IPTG induction, the recombinant protein was solubly expressed at a high level.