Elevated Interleukin-37 Associated with Dengue Viral Load in Patients with Dengue Fever.

Dengue remains a public health issue worldwide. Similar to chronic infectious diseases, stimulation of cytokine production is not enough to drive immune effector cells for effective virus clearance. One possible mechanism is the virus induces a large number of negative stimulatory cytokines inhibiting immune response. Interleukin 37 (IL-37) plays a crucial regulatory role in infection and immunity, inhibits innate and adaptive immunity as an anti-inflammatory cytokine by inhibiting proinflammatory mediators and pathways. To date, there are few studies reporting correlations between dengue fever (DF) and IL-37. In this study we found that the serum IL-37b and IL-37b-producing monocytes in patients were significantly increased in DF patients. A majority of the IL-37b produced by DF patients was produced by monocytes, not lymphocytes. Increased levels of IL-6, IL-10, and IFN-α were also found in DF patients. However, we failed to detect IL-1ß, IL-17A and TNF-α in plasma, because of off-target. In our study, there was no relation between IL-6, IL-10, and IFN-α expressions and IL-37b in serum (P > 0.05). The IL-37b-producing monocytes were negatively correlated with the level of IFN-α in serum and platelet count, and positively correlated with lymphocytes percentage (P < 0.05, respectively). Additionally, serum DENV nonstructural protein 1 levels were positively correlated with monocytes percentages (P < 0.05). Our data represents findings for IL-37b expression and its potential mechanisms in DF patients' immune response.

Ferroptosis: A mixed blessing for infectious diseases.

To date, it has been confirmed that the occurrence and development of infectious diseases are tightly associated with regulatory cell death processes, such as apoptosis, autophagy, and necroptosis. Ferroptosis, as a newly discovered form of regulatory cell death characterized by iron-dependent lipid peroxidation, is not only closely associated with tumor progression, but is also found to be tightly related to the regulation of infectious diseases, such as Tuberculosis, Cryptococcal meningitis, Malaria and COVID-2019. The emerging critical roles of ferroptosis that has been found in infectious disease highlight ferroptosis as a potential therapeutic target in this field, which is therefore widely expected to be developed into new therapy strategy against infectious diseases. Here, we summarized the underlying mechanisms of ferroptosis and highlighted the intersections between host immunity and ferroptosis. Moreover, we illuminated the roles of ferroptosis in the occurrence and progression of different infectious diseases, which might provide some unique inspiration and thought-provoking perspectives for the future research of these infectious diseases, especially for the development of ferroptosis-based therapy strategy against infectious diseases.

Immunomodulatory roles of selenium nanoparticles: Novel arts for potential immunotherapy strategy development.

Current chemotherapy strategies used in clinic appear with lots of disadvantages due to the low targeting effects of drugs and strong side effects, which significantly restricts the drug potency, causes multiple dysfunctions in the body, and even drives the emergence of diseases. Immunotherapy has been proved to boost the body's innate and adaptive defenses for more effective disease control and treatment. As a trace element, selenium plays vital roles in human health by regulating the antioxidant defense, enzyme activity, and immune response through various specific pathways. Profiting from novel nanotechnology, selenium nanoparticles have been widely developed to reveal great potential in anticancer, antibacterial, and anti-inflammation treatments. More interestingly, increasing evidence has also shown that functional selenium nanoparticles can be applied for potential immunotherapy, which would achieve more effective treatment efficiency as adjunctive therapy strategies for the current chemotherapy. By directly interacting with innate immune cells, such as macrophages, dendritic cells, and natural killer cells, selenium nanoparticles can regulate innate immunity to intervene disease developments, which were reported to boost the anticancer, anti-infection, and anti-inflammation treatments. Moreover, selenium nanoparticles can also activate and recover different T cells for adaptive immunity regulations to enhance their cytotoxic to combat cancer cells, indicating the potential of selenium nanoparticles for potential immunotherapy strategy development. Here, aiming to enhance our understanding of the potential immunotherapy strategy development based on Se NPs, this review will summarize the immunological regulation effects of selenium nanoparticles and the application of selenium nanoparticle-based immunotherapy strategies. Furthermore, we will discuss the advancing perspective of selenium nanoparticle-based potential immunotherapy as a kind of novel adjunctive therapy to enhance the efficiency of current chemotherapies and also introduce the current obstacles for the development of selenium nanoparticles for potential immunotherapy strategy development. This work is expected to promote the future research on selenium nanoparticle-assisted immunotherapy and finally benefit the more effective disease treatments against the threatening cancer and infectious and chronic diseases.

Molecular aggregation via partial Gal removal affects physicochemical and macromolecular properties of tamarind kernel polysaccharides.

The role of molecular aggregation was investigated on physicochemical and macromolecular properties of tamarind kernel polysaccharides via partial degalactosylation (TKPs vs. CTKPs). From the results, their main structural characteristics remained when partially degalactosylated, while primary aggregates as fundamental solution behavior were dynamically converted into higher aggregated forms. Micromorphologically, their conformational changes in different forms of crimping and aggregation could be further promoted by partial Gal removal to assemble on larger scales via hydrophobic interactions. Obviously, the aggregation role was unignorable, especially after partial degalactosylation, which affected TKPs and CTKPs differently concerning viscous behaviors, macromolecular characteristics, amorphous-crystalline transition and thermal stability, probably related to distinctiveness in polymerization degree, chemical structure, conformational entropy, solvent-solute interactions, specific intermolecular associations, etc. Therefore, molecular aggregation in tamarind kernel polysaccharides via specific Gal tailoring could be potential in applicable fields, such as postsurgical adhesion, packaging material design and plasma lipid metabolism.

Advances and Potentials of Polydopamine Nanosystem in Photothermal-Based Antibacterial Infection Therapies.

Bacterial infection remains one of the most dangerous threats to human health due to the increasing cases of bacterial resistance, which is caused by the extensive use of current antibiotics. Photothermal therapy (PTT) is similar to photodynamic therapy (PDT), but PTT can generate heat energy under the excitation of light of specific wavelength, resulting in overheating and damage to target cells or sites. Polydopamine (PDA) has been proved to show plenty of advantages, such as simple preparation, good photothermal conversion effects, high biocompatibility, and easy functionalization and adhesion. Taking these advantages, dopamine is widely used to synthesize the PDA nanosystem with excellent photothermal effects, good biocompatibility, and high drug loading ability, which therefore play more and more important roles for anticancer and antibacterial treatment. PDA nanosystem-mediated PTT has been reported to induce significant tumor inhibition, as well as bacterial killings due to PTT-induced hyperthermia. Moreover, combined with other cancer or bacterial inhibition strategies, PDA nanosystem-mediated PTT can achieve more effective tumor and bacterial inhibitions. In this review, we summarized the progress of preparation methods for the PDA nanosystem, followed by advances of their biological functions and mechanisms for PTT uses, especially in the field of antibacterial treatments. We also provided advances on how to combine PDA nanosystem-mediated PTT with other antibacterial methods for synergistic bacterial killings. Moreover, we further provide some prospects of PDA nanosystem-mediated PTT against intracellular bacteria, which might be helpful to facilitate their future research progress for antibacterial therapy.

Pectic polysaccharides from Biluochun Tea: A comparative study in macromolecular characteristics, fine structures and radical scavenging activities in vitro.

In this study, two acidic Biluochun Tea polysaccharides (BTP-A11 and BTP-A12) were investigated comparatively, which mainly consisted of Rha, Ara, Gal and GalA, possibly suggesting their pectic nature. Structurally, their galacturonan backbones composed of →4)-α-D-GalpA-(1→ and →2)-α-L-Rhap-(1→ were revealed similar, while Ara- and Gal-based branches attached to the O-2 of →2)-α-L-Rhap-(1→ were in distinctive types, proportions, extensibilities and branching degrees. This could lead to their different macromolecular characteristics, where BTP-A11 with higher Mw presented a more hyper-branched chain conformation and relatively higher structural flexibility/compactness, thereby resulting in a lower exclusion effect and an insufficient hydrodynamic volume. Besides, better radical scavenging activities in vitro were also determined for Gal-enriched BTP-A11, where a larger surface area containing more H-donating groups were related to its higher Mw, more hyper-branched conformation, lower DM and higher DA. Therefore, the understanding of structure-property-activity relationships was improved to some degrees for acidic Biluochun Tea polysaccharides, which could be potentially required for more applications in food, medical and cosmetic fields.

Engineering zinc oxide hybrid selenium nanoparticles for synergetic anti-tuberculosis treatment by combining Mycobacterium tuberculosis killings and host cell immunological inhibition.

Introduction: As a deadly disease induced by Mycobacterium tuberculosis (Mtb), tuberculosis remains one of the top killers among infectious diseases. The low intracellular Mtb killing efficiency of current antibiotics introduced the long duration anti-TB therapy in clinic with strong side effects and increased drug-resistant mutants. Therefore, the exploration of novel anti-TB agents with potent anti-TB efficiency becomes one of the most urgent issues for TB therapies. Methods: Here, we firstly introduced a novel method for the preparation of zinc oxide-selenium nanoparticles (ZnO-Se NPs) by the hybridization of zinc oxide and selenium to combine the anti-TB activities of zinc oxide nanoparticles and selenium nanoparticles. We characterized the ZnO-Se NPs by dynamic laser light scattering and transmission electron microscopy, and then tested the inhibition effects of ZnO-Se NPs on extracellular Mtb by colony-forming units (CFU) counting, bacterial ATP analysis, bacterial membrane potential analysis and scanning electron microscopy imaging. We also analyzed the effects of ZnO-Se NPs on the ROS production, mitochondrial membrane potential, apoptosis, autophagy, polarization and PI3K/Akt/mTOR signaling pathway of Mtb infected THP-1 macrophages. At last, we also tested the effects of ZnO-Se NPs on intracellular Mtb in THP-1 cells by colony-forming units (CFU) counting. Results: The obtained spherical core-shell ZnO-Se NPs with average diameters of 90 nm showed strong killing effects against extracellular Mtb, including BCG and the virulent H37Rv, by disrupting the ATP production, increasing the intracellular ROS level and destroying the membrane structures. More importantly, ZnO-Se NPs could also inhibit intracellular Mtb growth by promoting M1 polarization to increase the production of antiseptic nitric oxide and also promote apoptosis and autophagy of Mtb infected macrophages by increasing the intracellular ROS, disrupting mitochondria membrane potential and inhibiting PI3K/Akt/mTOR signaling pathway. Discussion: These ZnO-Se NPs with synergetic anti-TB efficiency by combining the Mtb killing effects and host cell immunological inhibition effects were expected to serve as novel anti-TB agents for the development of more effective anti-TB strategy.

Berberine-Loaded Biomimetic Nanoparticles Attenuate Inflammation of Experimental Allergic Asthma via Enhancing IL-12 Expression.

Asthma is one of the most common chronic pulmonary disorders, affecting more than 330 million people worldwide. Unfortunately, there are still no specific treatments for asthma so far. Therefore, it is very important to develop effective therapeutics and medicines to deal with this intractable disease. Berberine (Ber) has fabulous anti-inflammatory and antibacterial effects, while its low water solubility and bioavailability greatly limit its curative efficiency. To improve the nasal mucosa absorption of poorly water-soluble drugs, such as Ber, we developed a platelet membrane- (PM-) coated nanoparticle (NP) system (PM@Ber-NPs) for targeted delivery of berberine to the inflammatory lungs. In vivo, PM@Ber-NPs exhibited enhanced targeting retention in the inflammatory lungs compared with free Ber. In a mouse model of house dust mite- (HDM-) induced asthma, PM@Ber-NPs markedly inhibited lung inflammation, as evident by reduced inflammatory cells and inflammatory cytokines in the lung compared with free Ber. Collectively, our study demonstrated the inhibitory actions of nasally delivered nanomedicines on HDM-induced asthma, primarily through regulating Th1/Th2 balance by enhancing IL-12 expression which could potentially reduce lung inflammation and allergic asthma.

Inspirations of Cobalt Oxide Nanoparticle Based Anticancer Therapeutics.

Cobalt is essential to the metabolism of all animals due to its key role in cobalamin, also known as vitamin B12, the primary biological reservoir of cobalt as an ultra-trace element. Current cancer treatment strategies, including chemotherapy and radiotherapy, have been seriously restricted by their side effects and low efficiency for a long time, which urges us to develop new technologies for more effective and much safer anticancer therapies. Novel nanotechnologies, based on different kinds of functional nanomaterials, have been proved to act as effective and promising strategies for anticancer treatment. Based on the important biological roles of cobalt, cobalt oxide nanoparticles (NPs) have been widely developed for their attractive biomedical applications, especially their potential for anticancer treatments due to their selective inhibition of cancer cells. Thus, more and more attention has been attracted to the preparation, characterization and anticancer investigation of cobalt oxide nanoparticles in recent years, which is expected to introduce novel anticancer treatment strategies. In this review, we summarize the synthesis methods of cobalt oxide nanoparticles to discuss the advantages and restrictions for their preparation. Moreover, we emphatically discuss the anticancer functions of cobalt oxide nanoparticles as well as their underlying mechanisms to promote the development of cobalt oxide nanoparticles for anticancer treatments, which might finally benefit the current anticancer therapeutics based on functional cobalt oxide nanoparticles.

The Advancing of Selenium Nanoparticles Against Infectious Diseases.

Infectious diseases, caused by the direct exposure of cellular or acellular pathogens, are found to be closely associated with multiple inflammation and immune responses, keeping one of the top threats to human health. As an indispensable trace element, Selenium (Se) plays important roles in antioxidant defence and redox state regulation along with a variety of specific metabolic pathways. In recent decades, with the development of novel nanotechnology, Selenium nanoparticles (Se NPs) emerged as a promising agent for biomedical uses due to their low toxicity, degradability and high bioavailability. Taking the advantages of the strong ability to trigger apoptosis or autophagy by regulating reactive oxygen species (ROS), Se NPs have been widely used for direct anticancer treatments and pathogen killing/clearance in host cells. With excellent stability and drug encapsulation capacity, Se NPs are now serving as a kind of powerful nano-carriers for anti-cancer, anti-inflammation and anti-infection treatments. Notably, Se NPs are also found to play critical roles in immunity regulations, such as macrophage and T effector cell activation, which thus provides new possibilities to achieve novel nano-immune synergetic strategy for anti-cancer and anti-infection therapies. In this review, we summarized the progress of preparation methods for Se NPs, followed by the advances of their biological functions and mechanisms for biomedical uses, especially in the field of anti-infection treatments. Moreover, we further provide some prospects of Se NPs in anti-infectious diseases, which would be helpful for facilitating their future research progress for anti-infection therapy.

Macromolecular and thermokinetic properties of a galactomannan from Sophora alopecuroides L. seeds: A study of molecular aggregation.

The molecular aggregation of a galactomannan (NSAP-25) from Sophora alopecuroides L. seeds was investigated, where three polydisperse systems were confirmed during particle size analysis, indicating existence of different aggregates composed of random coil chains revealed by circular dichroism. Morphologically, NSAP-25 aggregate of various sizes (200-1200 nm) was possibly multi-stranded and formed by ellipsoid-like particles (20-60 nm) composed of compact coil chain, exhibiting extended amorphous structure with chain-like branches intertwined. Hence, NSAP-25 aggregation was inevitable, which exerted an unignorable effect on augmenting flexibility (ß↓, γ↓, α↓ and Lp/ML↓) and compactness (ρ↓, df↑ and C∞↓) of branched random coil chain based on macromolecular analysis, especially when concentration increased. Moreover, it could be relevant to thermokinetic behavior of random nucleation and subsequent growth (A2 model and negative ΔS*) as well as good thermal stability (IPDT, ITS, t0.05, Tm and Tp), thus conferring potential applications for NSAP-25 in food and pharmaceutical industries.

Circular RNA TRAPPC6B inhibits intracellular Mycobacterium tuberculosis growth while inducing autophagy in macrophages by targeting microRNA-874-3p.

OBJECTIVES: Genetic and epigenetic mechanisms regulate antimicrobial immunity against Mycobacterium tuberculosis (Mtb) infection. METHODS: The present study assessed circular RNA TRAPPC6B (circTRAPPC6B) for antimicrobial immune functions and defined mechanisms wherein circTRAPPC6B regulates Mtb growth, autophagy and microRNA in macrophages. RESULTS: The Mtb infection of monocytes/macrophages resulted in a significantly decreased level of circTRAPPC6B that inhibited intracellular Mtb growth in macrophages. Conversely, circTRAPPC6B expression enhanced autophagy or autophagy-associated protein LC3-II production in Mtb-infected macrophages. circTRAPPC6B-enhanced autophagy aggregation or sequestration was also observed in fluorescence in situ hybridisation (FISH) analysis and confocal imaging. Mechanistically, circTRAPPC6B targets an inhibiting element miR-874-3p, as shown by bioinformatics, dual-luciferase reporter gene analysis and pull-down assay, respectively. Notably, miR-874-3p prohibited autophagy via suppressing autophagy protein ATG16L1 by binding to its 3'-untranslated region (UTR) in Mtb-infected macrophages and thus promoting intracellular Mtb growth. Concurrently, circTRAPPC6B enhanced autophagy in Mtb-infected macrophages by blocking the ability of miR-874-3p to inhibit ATG16L1. Thus, circTRAPPC6B antagonises the ability of miR-874-3p to suppress ATG16L1 expression and activate and enhance autophagy sequestration to restrict Mtb growth in macrophages. CONCLUSION: The current findings suggested that both circTRAPPC6B and miR-874-3p mechanisms can be explored as potential therapeutics against Mtb infection.

[Corrigendum] CCL22 and IL­37 inhibit the proliferation and epithelial­mesenchymal transition process of NSCLC A549 cells.

Subsequently to the publication of the above paper, the authors have drawn to our attention that, owing to errors made in the compilation of the images in Fig. 6, the images shown in Fig. 6A­C in the article were selected incorrectly (essentially, the images shown in Fig. 6A and B were alterative presentations of the same data shown in Fig. 6C). The authors were able to re­examine the original data files and retrieve the correct data panels. The revised version of Fig. 6, featuring the corrected data panels for Fig. 6A­C, is shown opposite. Note that the revisions made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in Oncology Reports 36: 2017-2024, 2016; DOI: 10.3892/or.2016.4995].

Elevation in the counts of IL-35-producing B cells infiltrating into lung tissue in mycobacterial infection is associated with the downregulation of Th1/Th17 and upregulation of Foxp3+Treg.

IL-35 is an anti-inflammatory cytokine and is thought to be produced by regulatory T (Treg) cells. A previous study found that IL-35 was upregulated in the serum of patients with active tuberculosis (ATB), and IL-35-producing B cells infiltrated to tuberculous granuloma of patients with ATB. Purified B cells from such patients generated more IL-35 after stimulation by antigens of Mycobacterium tuberculosis and secreted more IL-10. However, the function and the underlying mechanisms of IL-35-producing B cells in TB progression have not been investigated. The present study found that the expression of mRNA of IL-35 subsets Ebi3 and p35 was elevated in mononuclear cells from peripheral blood, spleen, bone marrow, and lung tissue in a mouse model infected with Mycobacterium bovis BCG, as tested by real-time polymerase chain reaction. Accordingly, the flow cytometry analysis showed that the counts of a subset of IL-35+ B cells were elevated in the circulating blood and in the spleen, bone marrow, and lung tissue in BCG-infected mice, whereas anti-TB therapy reduced IL-35-producing B cells. Interestingly, BCG infection could drive the infiltration of IL-35-producing B cells into the lung tissue, and the elevated counts of IL-35-producing B cells positively correlated with the bacterial load in the lungs. Importantly, the injection of exogenous IL-35 stimulated the elevation in the counts of IL-35-producing B cells and was associated with the downregulation of Th1/Th17 and upregulation of Foxp3+Treg.The study showed that a subset of IL-35-producing B cells might take part in the downregulation of immune response in mycobacterial infection.

Circular RNA hsa_circ_0001380 in peripheral blood as a potential diagnostic biomarker for active pulmonary tuberculosis.

Numerous studies have suggested that circular RNAs (circRNAs), a type of non­coding RNA lacking 5'­caps and 3'­poly(A) tails, are involved in the biological processes of various human diseases. However, little is known about their functions and diagnostic value in active pulmonary tuberculosis (APTB). The aim of the present study was to examine whether hsa_circ_0001380 is able to serve as a diagnostic biomarker for patients with APTB. The expression level of hsa_circ_0001380 was detected in the peripheral blood of 32 patients with APTB and 31 healthy volunteers by reverse transcription­quantitative PCR. The functional prediction of hsa_circ_0001380 was performed in silico. RNase R was used to detect the stability of hsa_circ_0001380. Finally, the diagnostic value of hsa_circ_0001380 was evaluated by receiver operating characteristic (ROC) curve analysis. The results showed that hsa_circ_0001380 was significantly downregulated in the peripheral blood of patients with APTB. In addition, hsa_circ_0001380 was found to be resistant to RNase R treatment. Moreover, four N6­adenosine methylation modification sites and two potential microRNA binding sites were predicted in silico. Importantly, the area under the ROC curve was 0.9502, which suggested that hsa_circ_0001380 may act as a diagnostic biomarker for APTB. Taken together, the results indicated that circRNA hsa_circ_0001380 was downregulated in the peripheral blood of patients with APTB, and could serve as a diagnostic biomarker.

BTLA-Expressing Dendritic Cells in Patients With Tuberculosis Exhibit Reduced Production of IL-12/IFN-α and Increased Production of IL-4 and TGF-ß, Favoring Th2 and Foxp3+ Treg Polarization.

Little is known about how tuberculosis (TB) impairs dendritic cell (DC) function and anti-TB immune responses. We previously showed that the B and T lymphocyte attenuator (BTLA), an immune inhibitory receptor, is involved in TB pathogenesis. Here, we examined whether BTLA expression in TB affects phenotypic and functional aspects of DCs. Active TB patients exhibited higher expression of BTLA in myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) subsets compared with healthy controls (HCs). BTLA expression was similarly high in untreated TB, TB relapse, and sputum-bacillus positive TB, but anti-TB therapy reduced TB-driven increases in frequencies of BTLA+ DCs. BTLA+ DCs in active TB showed decreased expression of the DC maturation marker CD83, with an increased expression of CCR7 in mDCs. BTLA+ DCs in active TB displayed a decreased ability to express HLA-DR and to uptake foreign antigen, with a reduced expression of the co-stimulatory molecule CD80, but not CD86. Functionally, BTLA+ DCs in active TB showed a decreased production of IL-12 and IFN-α as well as a reduced ability to stimulate allogeneic T-cell proliferative responses. BTLA+ mDCs produced larger amounts of IL-4 and TGF-ß than BTLA- mDCs in both HCs and APT patients. BTLA+ DCs from active TB patients showed a reduced ability to stimulate Mtb antigen-driven Th17 and Th22 polarizations as compared to those from HCs. Conversely, these BTLA+ DCs more readily promoted the differentiation of T regulatory cells (Treg) and Th2 than those from HCs. These findings suggest that TB-driven BTLA expression in DCs impairs the expression of functional DC surrogate markers and suppress the ability of DCs to induce anti-TB Th17 and Th22 response while promoting Th2 and Foxp3+ Tregs.

Basic fibroblast growth factor blockade enhances lung cancer cell invasion by activating the AKT/MMP-2/VEGF pathway.

Basic fibroblast growth factor (bFGF) can stimulate cancer cell growth and invasion; however, the influence of bFGF blockade remains unclear. Therefore, we aimed to explore the effects of bFGF blockade on the growth and invasion in A549 (high bFGF expression) and H2122 (low bFGF expression) lung cancer cells. We found that the blocking of bFGF by a neutralizing monoclonal antibody suppressed the growth of A549 cells but not of H2122 cells, as well as strongly induced the invasiveness of A549 cancer cells. Furthermore, bFGF blockade activated the AKT pathway and enhanced the expression levels of matrix metalloproteinase (MMP)-2 and vascular endothelial growth factor (VEGF) in A549 cells. These responses could be reversed by treatment with AKT inhibitor and siMMP-2, thus indicating the involvement of the AKT/MMP-2/VEGF-positive feedback loop. Finally, we confirmed that the anti-bFGF-induced invasion of cancer cells could be rescued by inhibiting the AKT/MMP-2/VEGF loop. Our results revealed that bFGF blockade suppresses cell growth but promotes cell invasion in lung cancer cells with high bFGF expression levels. Our data further reinforced the importance of the AKT/MMP-2/VEGF loop in regulating anti-bFGF-induced tumour cell invasion and suggested the limitations of the bFGF-targeting strategy in lung cancer treatment.

High expression of BTLA and B7-H4 on the surface of myeloid dendritic cells has a negative regulatory effect on their anti-tuberculosis immunity activity in pleural tuberculosis patients.

To investigate the effects of the surface markers B- and T-lymphocyte attenuator (BTLA) and B7 homologous body 4 (B7-H4) on expression of CD83, and Human Leukocyte Antigen-DR isotype (HLA-DR) that can activate dendritic cells (DCs). Flow cytometry was used to detect the co-expression of BTLA and B7-H4 on myeloid DCs (mDCs) in peripheral blood (PB) and pleural effusions (PE) in 15 volunteers and 20 tuberculous pleurisy (TP) patients. Co-expression of BTLA and B7-H4 (double positive (DP)) mDCs in PB and PE of TP patients were enhanced. The proportion of DP mDC in PB decreased markedly after 2 weeks treatment, but was still greater than in controls. Expression of CD83 and HLA-DR on DP mDCs was higher than on BTLA and B7-H4 double negative (DN) expressing mDCs in PB of different TP groups. Expression of CD83 on DP mDCs in PB and PE of TP patients was greater than that of controls. Expression of HLA-DR on DP mDCs in TP patient PB was lower than in TP PE and controls. In pleural tuberculosis (TB) patients, high expression of BTLA and B7-H4 promoted a high level of CD83 and HLA-DR, which had a negative regulatory effect on mDCs on anti-TB immunity.

MTB driven B cells producing IL-35 and secreting high level of IL-10 in the patients with active pulmonary tuberculosis.

Regulatory B cells (Bregs) have critical roles as a negative regulator of immunity, mainly due to the fact that it secrets high a level of interleukin 10 (IL-10). Recently, a new subset of Bregs was identified as a key source of IL-35, which is an immunosuppressive cytokine and conventionally thought to be secreted by regulatory T cells (Tregs). Our previous study showed that the level of IL-35 in serum was elevated in the patients with active tuberculosis (ATB). However, none of the studies reported that IL-35 is secreted by B cells in ATB patients. In the current study, we found that the mRNA expressions of the both subunits (p35 and Ebi3) of IL-35 by circulating B cells were increased in ATB patients. By using immunohistochemistry and immunofluorescence staining, we found a subset of B cells infiltrated into the tuberculous granuloma of ATB patients also expressed IL-35. Moreover, Mycobacterium tuberculosis (MTB) lysate stimulation assay also demonstrated higher levels of IL-35 were exerted by MTB lysate within purified B cells from healthy control group (HC). Flow cytometry analysis further showed that the IL-35-producing B cells from ATB patients produced a higher level of IL-10. Taken together, IL-35-producing B cells may play a regulatory role during MTB infection by producing IL-10.

Role of B7-H4 in the Progression and Prognosis of Cervical Inflammation to Cancer After Human Papilloma Virus Infection.

The immune checkpoint molecule B7-H4 is highly expressed in various types of cancer, but little is known about its role in the development of cervical lesions associated with human papilloma virus (HPV). This study aimed to investigate the role of B7-H4 in cervical lesion progression and the relationship between B7-H4 and HPV infection. This was a retrospective study of tissue samples from 30 patients with cervical cancer, 28 with cervical intraepithelial neoplasia (CIN), and 75 with cervical inflammatory lesions. Serum-soluble B7-H4 (sB7-H4) was assessed by ELISA. Tissue B7-H4 expression was measured by RT-PCR and immunochemistry. Expression of B7-H4 in dendritic cells was assessed by flow cytometry. sB7H4 increased gradually from the patients with cervical inflammation to patients with cervical cancer and decreased after treatment. sB7-H4 had a diagnostic value in cervical intraepithelial neoplasia (CIN (area under the curve (AUC) = 0.8929) and cervical cancer (AUC = 0.9545). B7-H4 expression in inflammatory cervical tissue and peripheral blood dendritic cells (DCs) increased gradually from inflammation to cancer (P < 0.001). sB7-H4 was positively associated with B7-H4 expression in cervical tissue and DCs and with the frequency of CD4+CD25+Foxp3+ regulatory T cells (P < 0.001). The level of sB7-H4, and tissue and DC B7-H4 expression were associated with HPV infection (P < 0.001). These data strongly support the use of sB7-H4 for monitoring the progression of cervical cancer associated with HPV, and for evaluating the immune status of the patients.