Mycobacterium marinum mediates regulation of prostaglandin E2 expression on host immune response through cyclooxygenase pathway.

PURPOSE: Investigate the role of COX signaling in activating the PGE2-EP2 pathway. METHODS: Utilized a marine Mycobacterium infection model in zebrafish. Marine mycobacteria were stained with fluorescein isothiocyanate. The COX inhibitor indomethacin, EP2 receptor inhibitor AH6809, EP4 receptor inhibitor AH23848 and clodronate Liposomes were used to investigate the role of COX, EP2, EP4 and macrophage whether participating in combat marine mycobacterial infection. The expression level of the target gene was detected using real-time fluorescence quantitative PCR instrument. RESULTS: The findings revealed that larvae exposed to the COX inhibitor indomethacin or the EP2 receptor inhibitor AH6809 demonstrated a significantly higher mortality rate due to marine mycobacterium infection than those in the control group. Administration of exogenous prostaglandin E2 (PGE2) rescued the survival of zebrafish infected with marine mycobacteria and treated with indomethacin. Additionally, a significant reduction in survival rate was noted in macrophage-depleted zebrafish infected with marine mycobacteria. CONCLUSION: The host may combat marine mycobacterium infection via COX signaling, which activates the PGE2-EP2 pathway and mediates macrophage resistance.

Mass spectrometry-based identification of new serum biomarkers in patients with latent infection pulmonary tuberculosis.

Noninvasive and simple indicators for diagnosing latent tuberculosis (TB) infection (LTBI) and tracking progression from latent infection to active TB infection are still desperately needed. The aim of this study was to screen and identify possible biomarkers for diagnosing LTBI and monitoring the progression from latent infection to active TB infection, as well as to investigate the underlying processes and functions. To assess changes in metabolite composition associated with active tuberculosis infection in humans, whole blood supernatants were collected from patients with LTBI, drug-susceptible TB patients, drug-resistant TB patients, and healthy controls. The metabolites in all serum samples were extracted by oscillatory, deproteinization, and then detected by liquid chromatography-tandem mass spectrometry/MS analysis. Normalization by Pareto-scaling method, the difference analysis was carried out by Metaboanalyst 4.0 software, and 1-way analysis of variance analysis among groups showed that P-value < 0.05 was regarded as a different metabolite. To clarify the dynamic changes and functions of differential metabolites with disease progression, and explore its significance and mechanism as a marker by further cluster analysis, functional enrichment analysis, and relative content change analysis of differential metabolites. 65 metabolites were substantially different in four groups. Differential metabolites such as Inosine and Prostaglandin E1 may be important blood indicators for diagnosing mycobacterium tuberculosis latent infection, which were all tightly connected to amino acid metabolism, Biosynthesis of various secondary metabolites, Nucleotide metabolism, Endocrine system, Immune system, Lipid metabolism, and Nervous system. This study screened and identified Inosine, 16, 16-dimethyl-6-keto Prostaglandin E1, Theophylline, and Cotinine as potential serum biomarkers for diagnosing latent TB infection, and Cotinine as potential biomarkers for monitoring disease progression from healthy population to LTBI and then to active TB including drug-resistant TB infection and sensitive TB infection. Furthermore, this research provides a preliminary experimental basis to further investigate the development of metabolomics-based diagnosis of LTBI and monitoring the progress from latent infection to active TB infection.

Clonality, virulence genes, and antibiotic resistance of Staphylococcus aureus isolated from blood in Shandong, China.

BACKGROUND: Bloodstream infection (BSI) caused by Staphylococcus aureus (S. aureus) can be life-threatening and pose a great challenge to infection control and clinical treatment. However, little information exists regarding the characterization of S. aureus in BSI patients in Shandong, China. To identify the clonality, virulence genes, and antibiotic resistance of S. aureus in blood, a total of 101 nonrepetitive blood isolates were collected. The antibiotic resistance phenotypes were determined, and virulence genes were analyzed with polymerase chain reaction (PCR). Finally, the genetic relatedness was investigated with Staphylococcus chromosomal cassette mec (SCCmec) typing for methicillin-resistant S. aureus (MRSA) isolates, Staphylococcal protein A (spa), and multilocus sequence typing (MLST) for all of 101 isolates. RESULTS: Of the 101 S. aureus isolates, 24 MRSA isolates and 77 methicillin-susceptible S. aureus (MSSA) isolates were identified. Overall, MRSA isolates had higher resistance rates than MSSA isolates when exposed to any of the 15 antibiotics tested in this study except for trimethoprim/sulfamethoxazole. Among the 17 virulence genes tested in this study, hla, hld, and hlg could be detected in all isolates. MRSA isolates were more likely to carry seb and hlb genes, while MSSA isolates were more likely to carry seg and sei genes. Thirty-five sequence types (STs) and 49 spa types were identified, of which ST59-t437 and ST398-t571 were the most abundant. These two genotypes were also the most abundant ST-spa types in MRSA and MSSA isolates, but their abundances shifted over time, with ST398-t571 being the predominant genotype from 2016 to 2017, and ST59-t437 from 2018 to 2020. Besides, all the ST59-t437 isolates harbored hlgb gene, whereas most (88.9%) ST398-t571 did not. In addition, twenty-four MRSA isolates were subject to SCCmec typing. SCCmec IVa was the most prevalent SCCmec type, and all the ST59-t437 MRSA isolates were SCCmec IVa. We also observed 15 new STs, and some of them were MRSA. CONCLUSION: These findings provide additional observations and epidemiological data for blood S. aureus isolates, which can improve future infection-control measures and aid in potential clinical treatments in hospitals and other clinical settings.

Transcriptome Analysis of Peripheral Blood Mononuclear Cells Reveals Distinct Immune Response in Asymptomatic and Re-Detectable Positive COVID-19 Patients.

The existence of asymptomatic and re-detectable positive coronavirus disease 2019 (COVID-19) patients presents the disease control challenges of COVID-19. Most studies on immune responses in COVID-19 have focused on moderately or severely symptomatic patients; however, little is known about the immune response in asymptomatic and re-detectable positive (RP) patients. Here we performed a comprehensive analysis of the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from 48 COVID-19 patients which included 8 asymptomatic, 13 symptomatic, 15 recovered and 12 RP patients. The weighted gene co-expression network analysis (WGCNA) identified six co-expression modules, of which the turquoise module was positively correlated with the asymptomatic, symptomatic, and recovered COVID-19 patients. The red module positively correlated with symptomatic patients only and the blue and brown modules positively correlated with the RP patients. The analysis by single sample gene set enrichment analysis (ssGSEA) revealed a lower level of IFN response and complement activation in the asymptomatic patients compared with the symptomatic, indicating a weaker immune response of the PBMCs in the asymptomatic patients. In addition, gene set enrichment analysis (GSEA) analysis showed the enrichment of TNFα/NF-κB and influenza infection in the RP patients compared with the recovered patients, indicating a hyper-inflammatory immune response in the PBMC of RP patients. Thus our findings could extend our understanding of host immune response during the progression of COVID-19 disease and assist clinical management and the immunotherapy development for COVID-19.

Sputum microbiota as a potential diagnostic marker for multidrug-resistant tuberculosis.

The prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains makes disease control more complicated, which is the main cause of death in tuberculosis (TB) patients. Early detection and timely standard treatment are the key to current prevention and control of drug-resistant TB. In recent years, despite the continuous advancement in drug-resistant TB diagnostic technology, the needs for clinical rapid and accurate diagnosis are still not fully met. With the development of sequencing technology, the research of human microecology has been intensified. This study aims to use 16 rRNA sequencing technology to detect and analyze upper respiratory flora of TB patients with anti-TB drug sensitivity (DS, n = 55), monoresistance isoniazide (MR-INH, n = 33), monoresistance rifampin (MR-RFP, n = 12), multidrug resistance (MDR, n = 26) and polyresistance (PR, n = 39) in southern China. Potential microbial diagnostic markers for different types of TB drug resistance are searched by screening differential flora, which provides certain guiding significance for drug resistance diagnosis and clinical drug use of TB. The results showed that the pulmonary microenvironment of TB patients was more susceptible to infection by external pathogens, and the infection of different drug-resistant Mtb leads to changes in different flora. Importantly, seven novel microorganisms (Leptotrichia, Granulicatella, Campylobacter, Delfitia, Kingella, Chlamydophila, Bordetella) were identified by 16S rRNA sequencing as diagnostic markers for different drug resistance types of TB. Leptotrichia, Granulicatella, Campylobacter were potential diagnostic marker for TB patients with INH single-resistance. Delftia was a potential diagnostic marker for TB patients with RFP single drug-resistance. Kingella and Chlamydophila can be used as diagnostic markers for TB patients with PR. Bordetella can be used as a potential diagnostic marker for identification of TB patients with MDR.

Tandem Mass Tag-Based Proteomic Analysis of Potential Biomarkers for Hepatocellular Carcinoma Differentiation.

PURPOSE: The poor prognosis of hepatocellular carcinoma (HCC) urgent us to discover early and effective biomarkers. In this study, we applied tandem mass tag (TMT)-based proteomic analysis to discover potential protein markers for HCC identification and differentiation. PATIENTS AND METHODS: Fifteen patients, well-differentiated (G1, N = 5), moderate-differentiated (G2, N = 5), and poorly differentiated (G3, N = 5), with 30 matched pair tissues (both tumor and adjacent non-tumor tissues derived from the same patient) were enrolled. All samples were subjected to TMT labeling and LC-MS/MS analysis. The identified proteins were subsequently assigned to GO and KEGG for predicting function. The identified protein candidates were validated using immunohistochemistry (IHC). RESULTS: A total of 1010 proteins were identified. Of these, 154 differentially expressed proteins (DEPs), 100 up-regulated and 54 down-regulated, were found between tumor and adjacent non-tumor tissues; 12 DEPs, 9 up-regulated and 3 down-regulated, were found between G1 and G3 tissues; 8 DEPs, 5 up-regulated and 3 down-regulated, were found between G1 and G2 tissues; 11 DEPs, 8 up-regulated and 3 down-regulated, were found between G2 and G3 tissues. Among them, ASS1 and CPS1 were significantly up-regulated while UROD and HBB were significantly down-regulated in G3 compared with G1 and G2 tumors. Three proteins, CYB5A, FKBP11 and YBX1, were significantly up-regulated in G1 compared with both G2 and G3 tumors. The 7 biomarker candidates were further verified by IHC. CONCLUSION: A variety of DEPs related to the histological differentiation of HCC were identified, among which ASS1, CPS1, URPD and HBB proteins were potential biomarkers for distinguishing poorly differentiated HCC, while CYB5A, FKBP11 and YBX1 were potential biomarkers for distinguishing well-differentiated HCC. Our findings may further provide a new insight facilitating the diagnosis and prognosis of HCC.

T-Cell Repertoire Characteristics of Asymptomatic and Re-Detectable Positive COVID-19 Patients.

The prevention of the COVID-19 pandemic is highly complicated by the prevalence of asymptomatic and recurrent infection. Many previous immunological studies have focused on symptomatic and convalescent patients, while the immune responses in asymptomatic patients and re-detectable positive cases remain unclear. Here we comprehensively analyzed the peripheral T-cell receptor (TCR) repertoire of 54 COVID-19 patients in different courses, including asymptomatic, symptomatic, convalescent, and re-detectable positive cases. We identified a set of V-J gene combinations characterizing the upward immune responses through asymptomatic and symptomatic courses. Furthermore, some of these V-J combinations could be awakened in the re-detectable positive cases, which may help predict the risk of recurrent infection. Therefore, TCR repertoire examination has the potential to strengthen the clinical surveillance and the immunotherapy development for COVID-19.

Aberrant expression of miR-16, B12 and CD272 in peripheral blood mononuclear cells from patients with active tuberculosis.

Tuberculosis (TB) immunity is affected by complex immune regulation processes, which involve various immune cells, immune molecules, and cytokines. Here, we evaluated the expression of B12, CD272 and miR-16 in peripheral blood mononuclear cells (PBMC) of patients with active pulmonary tuberculosis. The results showed that monocytes expressing CD272 or B12 were down-regulated in patients with tuberculosis. The expression of B12 and CD272 in T cells and monocytes is related to tuberculosis. In TB patients, the up-regulation of miR-16 was negatively correlated with B12 mRNA expression, miR-16 was mainly expressed in CD14+ monocytes, and CD272 mRNA was mainly expressed in CD19+ B cells. It is worth noting that the overexpression of miR-16 inhibits the expression of CD272 and B12 in monocytes of TB patients. After BCG stimulation, miR-16 expression of CD14+ monocytes was up-regulated and B12 mRNA and CD272 mRNA expressions were down-regulated in TB patients. Finally, we found that miR-16 may participate in the TB immunization process through targeted regulation of B12 expression. These studies indicate that the expression of B12, CD272 and miR-16 in PBMC may be related to tuberculosis.

Preparation, Characterization, and Release Behavior of Doxorubicin hydrochloride from Dual Cross-Linked Chitosan/Alginate Hydrogel Beads.

With double cross-linking of chitosan (CS) and sodium alginate (SALG), a colon-targeting CS/SALG hydrogel bead was prepared and used for the colon-targeted release of doxorubicin hydrochloride (DOX). The CS/SALG hydrogel bead showed the improved mechanical property to withstand the simulated colon intestinal fluid (SCF), small intestinal fluid (SIF), as well as gastric fluid (SGF). DOX was released slightly in SGF and SIF and rapidly in SCF, showing a controlled DOX release from the CS/SALG hydrogel bead under different physiological conditions. In vitro cytotoxicity and in vivo toxicity assays indicated that the DOX-loaded CS/SALG hydrogel bead displayed obvious inhibition to tumor cells. These results suggested that the CS/SALG hydrogel bead had the potential application as a colon-targeting oral formulation for DOX transport.

[Mass spectrometry-based identification of new serum biomarkers in patients with multidrug resistant pulmonary tuberculosis].

OBJECTIVE: To screen new serum metabolic biomarkers for different drug resistance profiles of pulmonary tuberculosis (TB) and explore their mechanisms and functions. METHODS: We collected serum samples from TB patients with drug sensitivity (DS), monoresistance to isoniazid (MR-INH), monoresistance to rifampin (MR-RFP), multidrug resistance (MDR), and polyresistance (PR). The metabolites in the serum samples were extracted by oscillatory and deproteinization for LC-MS/MS analysis, and the results were normalized by Pareto-scaling method and analyzed using Metaboanalyst 4.0 software to identify the differential metabolites. The differential metabolites were characterized by function enrichment and co-expression analysis to explore their function and possible pathological mechanisms. RESULTS: Compared with the DS group, 286 abnormally expressed metabolites were identified in MR-INH group, 362 in MR-RPF group, 277 in MDR group and 1208 in PR group by LC-MS/MS analysis. Acetylagmatine (P < 0.05), aminopentol (P < 0.05), and tetracosanyl oleate (P < 0.05) in MR-INH group; Ala His Pro Thr (P < 0.001) and glycinoprenol-9 (P < 0.05) in MR-RFP group; trimethylamine (P < 0.05), penaresidin A (P < 0.05), and verazine (P < 0.05) in MDR group; and PIP (18:1(11Z)/ 18:3(6Z, 9Z, 12Z)) (P < 0.001), Pro Arg Trp Tyr (P < 0.001), N-methyldioctylamine (P < 0.001), and phytolaccoside E (P < 0.05) in PR group all showed significant differential expressions. Significant differential expressions of phthalic acid mono-2-ethylhexyl ester (P < 0.05) and eicosanoyl-EA (P < 0.05) were found in all the drug resistant groups as compared with DS group. CONCLUSIONS: Acetylagmatine, aminopentol, tetracosanyl oleate, Ala His Pro Thr, glycinoprenol-9, trimethylamine, penaresidin A, verazine, PIP(18:1(11Z)/18:3(6Z, 9Z, 12Z)), Pro Arg Trp Tyr, N-methyldioctylamine, phytolaccoside E, phthalic acid mono-2-ethylhexyl ester, and eicosanoyl-EA are potentially new biomarkers that indicate monoresistance, multi-drug resistance and polyresistance of Mycobacterium tuberculosis. The combined use of these biomarkers potentially allows for assessment of drug resistance in TB and enhances the diagnostic sensitivity and specificity.

Upregulation of miR-196b-5p attenuates BCG uptake via targeting SOCS3 and activating STAT3 in macrophages from patients with long-term cigarette smoking-related active pulmonary tuberculosis.

BACKGROUND: Cigarette smoking (CS) triggers an intense and harmful inflammatory response in lungs mediated by alveolar and blood macrophages, monocytes, and neutrophils and is closely associated with prevalence of tuberculosis (TB). The risk of death in patients with long-term cigarette smoking-related pulmonary tuberculosis (LCS-PTB) is approximately 4.5 times higher than those with nonsmoking pulmonary tuberculosis (N-PTB). However, the mechanisms underlying the harmful inflammatory responses in the setting of LCS-PTB have not been well documented. METHODS: 28 cases LCS-PTB patients, 22 cases N-PTB patients and 20 cases healthy volunteers were enrolled in this study. Monocytes were isolated from peripheral blood mononuclear cells. Differentiated human MDM and U937 cell were prepared with M-CSF and PMA stimulation, respectively. The miR-196b-5p, STAT1, STAT3, STAT4, STAT5A, STAT5B, STAT6, SOCS1 and SOCS3 mRNA expression were detected by qRT-PCR. Western blot was performed according to SOCS1, SOCS3, and pSTAT3 expression. The mycobacterial uptake by MDMs from different groups of patients after Bacillus Calmette-Guérin (BCG) infection and agomir-196b-5p or antagomir-196b-5p transfection were used by flow cytometry analysis. Human IL-6, IL-10 and TNF-α levels on the plasma and cell culture supernatant samples were measured using ELISA. For dual-luciferase reporter assay, the SOCS3 3'-UTR segments, containing the binding elements of miR-196b-5p or its mutant versions were synthesized as sense and antisense linkers. RESULTS: In this study, we found that IL-6, TNF-α production, SOCS3 mRNA expression were downregulated, while miR-196b-5p and STAT3 mRNA expression were upregulated in monocytes from LCS-PTB patients as compared to N-PTB patients. Meanwhile, we demonstrated that miR-196b-5p could target SOCS3 and activate STAT3 signaling pathway, which may possibly contribute to attenuation of BCG uptake and decrease in IL-6 and TNF-α production in macrophages. CONCLUSIONS: Our findings revealed that CS exposure regulates inflammatory responses in monocyte/macrophages from LCS-PTB patients via upregulating miR-196b-5p, and further understanding of the specific role of miR-196b-5p in inflammatory responses mightfacilitate elucidating the pathogenesis of LCS-PTB, thus leading to the development of new therapeutic strategies for PTB patients with long-term cigarette smoking.

Bacillus Calmette Guérin (BCG) activates lymphocyte to promote autophagy and apoptosis of gastric cancer MGC-803 cell.

Bacillus Calmette Guérin (BCG) has a potential anti-tumor effect on gastric cancer. However, the mechanism is still unclear. In this study, we investigated the effect of BCG on gastric cancer cell line MGC-803 and studied the potential cooperation of BCG and lymphocyte in determining the final fate of cancer cells. After treatment with BCG, the cell viability was significantly inhibited in a dosage-dependent manner. Flow cytometry assay showed the apoptosis rates were significantly increased by BCG. Using western blot assay, results showed that BCG increased cleaved-caspase-3, LC-3BII and Atg-3. After cocultured with BCG and lymphocyte, the apoptosis rates, the levels of cleaved-caspase-3, and the protein levels of LC-3BII and Atg-3 were significantly increased compared with BCG or lymphocytes alone groups. ELISA detection found that BCG induced secretion of interferon gamma (IFNg) from lymphocytes. BCG with IFNg also increased levels of cleaved-caspase-3, LC-3BII and Atg-3. Taken together, BCG promotes lymphocyte immunocompetence to induce cell apoptosis and autophagy in MGC-803 cells, might through inducing release of IFNg from peripheral blood lymphocytes.

Tuberculous pleurisy drives marked effector responses of γδ, CD4+, and CD8+ T cell subpopulations in humans.

Although tuberculous pleurisy (TP) presumably involves a hypersensitivity reaction, there is limited evidence indicating overreactive effector responses of γδ T cells and αß T cells and their interrelation with Foxp3(+) Tregs in pleural and other compartments. We found that TP induced reciprocal representations of Foxp3(+) Tregs and Mtb phosphoantigen-specific Vγ2Vδ2 T cells in different anatomic compartments. Patients with TP exhibited appreciable numbers of "proliferating" Ki-67(+) Vγ2Vδ2 T cells in the airway where Foxp3(+) Tregs were not dominant, whereas striking increases in Foxp3(+) Tregs in the blood and pleural compartments coincided with low frequencies of Vγ2Vδ2 T cells. Interestingly, anti-tuberculosis chemotherapy control of Mtb infection in patients with TP reversed reciprocal representations of Foxp3(+) Tregs and proliferating Vγ2Vδ2 T cells. Surprisingly, despite high-level Foxp3(+) Tregs, TP appeared to drive overreactive responses of IFN-γ-producing Vγ2Vδ2, CD4(+)CD25(+), and CD8(+)CD25(+) T effector subpopulations, whereas IL-22-producing Vγ2Vδ2 T cells increased subtly. Th1 effector responses were sustained despite remarkable declines in Foxp3(+) Tregs at 1 mo after the treatment. Overreactive T effector responses of Mtb-reactive γδ T cells, αß CD25(+)CD4(+), and CD25(+)CD8(+) T cell subpopulations appear to be immune features for TP. Increased Foxp3(+) Tregs might be responsive to overreactive TP but unable to influence T effector responses despite having an inverse relation with proliferating Vγ2Vδ2 T cells.

Elevated HMGB1-related interleukin-6 is associated with dynamic responses of monocytes in patients with active pulmonary tuberculosis.

There were limited studies assessing the role of HMGB1 in TB infection. In this prospective study, we aimed to assess the levels of HMGB1 in plasma or sputum from active pulmonary tuberculosis (APTB) patients positive for Mtb culture test, and to evaluate its relationship with inflammatory cytokines and innate immune cells. A total of 36 sputum Mtb culture positive APTB patients and 32 healthy volunteers (HV) were included. Differentiated THP-1 cells were treated for 6, 12 and 24 hrs with BCG at a multiplicity of infection of 10. The absolute values and percentages of white blood cells (WBC), neutrophils, lymphocytes, and monocytes were detected by an automatic blood analyzer. Levels of HMGB1, IL-6, IL-10 and TNF-α in plasma, sputum, or cell culture supernatant were measured by ELISA. The blood levels of HMGB1, IL-6, IL-10 and TNF-α, the absolute values of WBC, monocytes and neutrophils, and the percentage of monocytes were significant higher in APTB patients than those in HV groups (P < 0.05). The sputum levels of HMGB1, IL-10, and TNF-α were also significantly higher in APTB patients than those in HV groups (P < 0.05). Meanwhile, plasma level of HMGB1, IL-6, and IL-10 in APTB patients were positively correlated with those in sputum (P < 0.05), respectively. IL-6 was positively correlated with HMGB1 both in plasma and sputum of APTB patients (P < 0.05). HMGB1 and IL-6 is positively correlated with the absolute number of monocytes in APTB patients (P < 0.05). BCG induced HMGB1, IL-6, IL-10 and TNF-α production effectively in PMA-treated THP-1 cells. HMGB1 may be used as an attractive biomarker for APTB diagnosis and prognosis and may reflect the inflammatory status of monocytes in patients with APTB.

[The early warning and prognostic value of serum soluble TREM-1 for active pulmonary tuberculosis].

OBJECTIVE: To investigate the role of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in patients with active pulmonary tuberculosis (ATB) and explore its clinical significance. METHODS: The study included 78 cases of ATB patients and 40 cases of healthy volunteers from Dongguan Hospital for Chronic Diseases. Peripheral blood neutrophils and monocytes were counted by automated hematology analyzer. Serum sTREM-1 levels were detected by ELISA, and then the relevance with neutrophils and monocytes were analyzed by Pearson correlation test, respectively. RESULTS: The absolute numbers of neutrophils and monocytes, and the levels of serum sTREM-1 were higher in ATB patients than those in normal controls. In smear positive patients, the absolute numbers of neutrophils and monocytes, and the levels of serum sTREM-1 were higher than those in smear negative patients. The absolute numbers of neutrophils and monocytes, and the levels of serum sTREM-1 decreased in ATB patients after anti-TB drug treatments. Serum sTREM-1 level ≥ 528.14 pg/mL was very useful to diagnosis the smear positive ATB, and the accuracy was 100%. Pearson correlation test revealed that the absolute numbers of neutrophils and monocytes were both positively correlated to the levels of serum sTREM-1. CONCLUSION: High serum levels of sTREM-1 may be of high value for early warning and prediction of poor prognosis in ATB patients.

BTLA exhibits immune memory for αß T cells in patients with active pulmonary tuberculosis.

Despite past extensive studies, the role of B and T lymphocyte attenuator (BTLA) in αß T cells in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here we demonstrate that BTLA expression on αß T cells is decreased in patients with M. tuberculosis (Mtb) infection. Particularly, BTLA expression levels are likely critical for αß T cells to manifest and maintain an active central memory phenotype with high capacity for secretion of IFN-γ and perforin, which are important for immune memory against TB infection. BTLA(high) αß T cells also exhibited higher capacity in response to Mtb peptide stimulation. In contrast to the role of BTLA played for negative regulation of immune responses, our data in the current studies suggest that BTLA expression on αß T cells is likely associated with protective immune memory against Mtb infection in the setting of patients with active pulmonary tuberculosis. This previous unappreciated role for BTLA may have implications for prevention and treatment of patients with Mtb infection.

[Association of filaggrin gene polymorphism with atopic dermatitis in southern Chinese Han population].

OBJECTIVE: To investigate the association of filaggrin gene (FLG) polymorphism with atopic dermatitis (AD) in southern Chinese Han population. METHODS: The frequencies of the 13 known FLG gene single nucleotide polymorphism(SNPs), including 3321delA, 441delA, 1249insG, E1795X, S3296X, R501X, 2282del4, R2447X, S2889X, 7945delA, 3702delG, Q2417X, R4307X, were detected in a cohort of 50 AD patients and 100 control individuals using polymerase chain reaction (PCR) and DNA sequencing. RESULTS: FLG 3321delA and 441delA were detected in 14 (28%) and 6 (12%) AD patients, respectively. The other 11 SNPs were not detected in the patients. None of the 13 SNPs was detected in the controls. CONCLUSION: The results suggested that the FLG gene might be associated with atopic dermatitis susceptibility in southern Chinese Han population.

Structure and function of the NS1 protein of influenza A virus.

The avian influenza A virus currently prevailing in Asia causes fatal pneumonia and multiple organ failure in birds and humans. Despite intensive research, understanding of the characteristics of influenza A virus that determine its virulence is incomplete. NS1A protein, a non-structural protein of influenza A virus, was reported to contribute to its pathogenicity and virulence. NS1A protein is a multifunctional protein that plays a significant role in resisting the host antiviral response during the influenza infection. This review briefly outlines the current knowledge on the structure and function of the NS1A protein.