γδ T Cells Provide Protective Function in Highly Pathogenic Avian H5N1 Influenza A Virus Infection

Given the high mortality rate (>50%) and potential danger of intrapersonal transmission, highly pathogenic avian influenza (HPAI) H5N1 epidemics still pose a significant threat to humans. γδ T cells, which participate on the front line of the host immune defense, demonstrate both innate, and adaptive characteristics in their immune response and have potent antiviral activity against various viruses. However, the roles of γδ T cells in HPAI H5N1 viral infection remain unclear. In this study, we found that γδ T cells provided a crucial protective function in the defense against HPAI H5N1 viral infection. HPAI H5N1 viruses could directly activate γδ T cells, leading to enhanced CD69 expression and IFN-γ secretion. Importantly, we found that the trimer but not the monomer of HPAI H5N1 virus hemagglutinin (HA) proteins could directly activate γδ T cells. HA-induced γδ T cell activation was dependent on both sialic acid receptors and HA glycosylation, and this activation could be inhibited by the phosphatase calcineurin inhibitor cyclosporin A but not by the phosphatidylinositol 3-kinase (PI3-K) inhibitors wortmannin and LY294002. Our findings provide a further understanding the mechanism underlying γδ T cell-mediated innate and adoptive immune responses against HPAI H5N1 viral infection, which helps to develop novel therapeutic strategies for the treatment of H5N1 infection in the future

The Mechanism of Delayed Ischemic Preconditioning in Alleviating Acute Ischemia/Reperfusion Renal Injury through Treg Mediated by Immature CD11c+ Dendritic Cells

Introduction: Renal ischemia-reperfusion injury (IRI) is one of the major causes of acute kidney injury, and its mechanism is complex involving multiple factors, while delayed ischemic preconditioning (DIPC) has a protective effect on the above process. In our previous study, we found that DIPC can exert its protection on renal IRI by inhibiting the maturation of dendritic cells (DCs), but the mechanism has not been clarified. This study aimed to investigate the protective mechanism of DIPC on renal IRI in mice through Treg mediated by immature DCs (imDCs). Methods: The IRI mice model, DIPC treatment, and conditional CD11c+ DCs (CD11c-DTR) knockout mice were used to perform our study. The maturation and differentiation of DCs and Treg cells in the kidney and spleen were analyzed by flow cytometry. HE staining was used to evaluate the pathology of the kidney tissue. The level of creatinine (Cr), oxidative stress factors (SOD, MDA), and inflammatory factors (TNF-α, IL-10, IL-4) were also measured. Then, imDCs were co-cultured with HK-2 cells, and apoptosis was analyzed with flow cytometry and PI-Hoechst 33,342 fluorescence staining to assess the apoptosis rate of HK-2 cells under hypoxic-reoxygenated (H/R) conditions. Results: DIPC could decrease renal Cr levels, alleviate pathological renal damage, and reduce oxidative stress and inflammation caused by IRI. Moreover, DIPC could decrease the number of mature DCs (mDCs) and increase Treg lymphocyte infiltration in the kidney tissue, while the reduction of DCs reversed this process. In addition, our in vitro experiment found that in the H/R model, the apoptosis of HK-2 cells decreased which were co-cultured with imDCs. Conclusion: DIPC can regulate the differentiation of DCs into imDCs, thus affecting the differentiation level and distribution of Treg cells to exert its protective effect on renal IRI

Probing Temperature- and pH-Dependent Binding between Quantum Dots and Bovine Serum Albumin by Fluorescence Correlation Spectroscopy

Luminescent quantum dots (QDs) with unique optical properties have potential applications in bio-imaging. The interaction between QDs and bio-molecules is important to the biological effect of QDs in vivo. In this paper, we have employed fluorescence correlation spectroscopy (FCS) to probe the temperature- and pH-dependent interactions between CdSe QDs with carboxyl (QDs-COOH) and bovine serum albumin (BSA) in buffer solutions. The results have shown that microscopic dissociation constant K′D is in the range of (1.5 ± 0.2) × 10−5 to (8.6 ± 0.1) × 10−7 M, the Hill coefficient n is from 0.4 to 2.3, and the protein corona thickness is from 3.0 to 9.4 nm. Variable-temperature measurements have shown both negative values of ∆H and ∆S for BSA adsorption on QDs-COOH, while pH has a profound effect on the adsorption. Additional, FCS measurement QDs-COOH and proteins in whole mice serum and plasma samples has also been conducted. Finally, simulation results have shown four favored QD binding sites in BSA

Electromagnetic reprogrammable coding-metasurface holograms

Metasurfaces have enabled a plethora of emerging functions within an ultrathin dimension, paving way towards flat and highly integrated photonic devices. Despite the rapid progress in this area, simultaneous realization of reconfigurability, high efficiency, and full control over the phase and amplitude of scattered light is posing a great challenge. Here, we try to tackle this challenge by introducing the concept of a reprogrammable hologram based on 1-bit coding metasurfaces. The state of each unit cell of the coding metasurface can be switched between '' and '' by electrically controlling the loaded diodes. Our proof-of-concept experiments show that multiple desired holographic images can be realized in real time with only a single coding metasurface. The proposed reprogrammable hologram may be a key in enabling future intelligent devices with reconfigurable and programmable functionalities that may lead to advances in a variety of applications such as microscopy, display, security, data storage, and information processing.National Natural Science Foundation of China [61471006, 61631007, 61571117]; 111 Project [111-2-05]; National Research Foundation, Prime Minister's Office, Singapore, under its Competitive Research Programme (CRP Award) [NRF-CRP15-2015-03]; ERC consolidator grant (TOPOLOGICAL); Royal Society; Wolfson Foundation; Leverhulme [RPG-2012-674]SCI(E)ARTICLE

Gene verification with real-time quantitative PCR.

<p>Several genes from Vγ1⁺ and Vγ4⁺ γδ T cells were selected for verification against biological replicates using real-time quantitative PCR (A-E). Expression data for each gene were normalized against β-actin. Data shown are the means ± SD (error bars). (* p≤0.05, ** p≤0.01, *** p≤0.001, unpaired two-tailed Student’s t-test). Data are representative of three independent experiments.</p

Gene-specific primers for real-time quantitative PCR.

<p>Gene-specific primers for real-time quantitative PCR.</p

The distribution of gene expression.

<p>The ‘x’ axis represents Log fold-change of differentially expressed genes. The ‘y’ axis represents number of genes. Red region represents genes with expression within 4-fold change; green and blue regions represent genes with more than 4-fold change either up or down regulated, respectively. Library pairs: A, resting Vγ1⁺ vs activated Vγ1⁺ γδ T cells; B, resting Vγ4⁺ vs activated Vγ4⁺ γδ T cells.</p

Sequencing reads and mapping rates of each sample.

<p>γ1-PBS, Vγ1⁺ γδ T cells treated with PBS; γ1-PMA/Ion, Vγ1⁺ γδ T cells treated with PMA and Ionomycin; γ4-PBS, Vγ4⁺ γδ T cells treated with PBS; γ4-PMA/Ion, Vγ4⁺ γδ T cells treated with PMA and Ionomycin.</p><p>Sequencing reads and mapping rates of each sample.</p

Cytokines secreted by Vγ1⁺ and Vγ4⁺ γδ T cells.

<p>Both subsets of γδ T cells produce IFN-γ, TNFα, TGF-β and IL-10. Vγ1+ γδ T cells tend to produce Th2 type cytokines IL-4 and IL-5 while Vγ4⁺ γδ T cells tend to produce IL-17.</p