Bones on fire: illuminating osteomyelitis through the radiant lens of 18F-FDG PET/CT.

Osteomyelitis is an inflammatory process that is caused by an infecting microorganism and leads to progressive bone destruction and loss. Osteomyelitis can occur at any age and can involve any bone. The infection can be limited to a single portion of the bone or can involve several regions, such as marrow, cortex, periosteum, and the surrounding soft tissue. Early and accurate diagnosis plays a crucial role in reducing unnecessary treatment measures, improving the patient's prognosis, and minimizing time and financial costs. In recent years, the use of functional metabolic imaging has become increasingly widespread. Among them, 18F-FDG PET/CT has emerged as a cutting-edge imaging modality that combines anatomical and functional metabolic information. It has seen rapid development in the field of infectious diseases. 18F-FDG PET/CT has been demonstrated to yield acceptable diagnostic accuracy in a number of infectious and inflammatory diseases. This review aims to provide information about the 18F-FDGPET/CT in the use of chronic osteomyelitis,osteomyelitis secondary to a contiguous focus of infection and osteomyelitis associated with peripheral vascular disease.

Avasimibe can cooperate with a DC-targeting and integration-deficient lentivector to induce stronger HBV specific T cytotoxic response by regulating cholesterol metabolism.

We have reported a lentivector which could effectively induce HBV-specific cytotoxic T lymphocytes (CTLs). Avasimibe is an inhibitor of acetyl-CoA acetyltransferase-1 (ACAT1), and has been shown to enhance T lymphocyte cytotoxicity on tumor cells. However, the role of avasimibe in lentivector-induced HBV-specific T cytotoxic response remains unknown. Based on previous study, we constructed an integration-deficient lentivector LVDC-ID-HBV (harboring HBcAg expression), and the in vitro experiments showed that the combination of avasimibe exhibited better efficacy in inducing HBV-specific CTL responses including cell proliferation, production of cytokines, as well as CTL killing activities. Mechanism experiments showed that increasing cell membrane cholesterol levels by MßCD-coated cholesterol or ACAT1 inhibition efficiently promoted TCR clustering, signaling transduction and immunological synapse formation, thereby mediating augmented CTL responses. Nevertheless, the depletion of plasma membrane cholesterol with MßCD led to obviously decreased CTL responses. The avasimibe-mediated strengthened immune effects were also determined in animal experiments and the results were in agreement with those from the in vitro research. In particular, the in vivo CTL killing activities were identified by the CFSE or BV-labeled splenocyte lysis assay. Moreover, the experiments in HBV transgenic mice showed that the LVDC-ID-HBV plus avasimibe group demonstrated the lowest serum HBsAg and HBV DNA levels, as well as the lowest expression of HBsAg and HBcAg in liver tissues. We concluded that the HBV-specific CTL immune responses could be potentiated by avasimibe through regulating plasma membrane cholesterol levels. Avasimibe may be a potential adjuvant for lentivector vaccine against HBV infection.

Exosomes loading Tapasin enhance T cell immune response by autophagy to inhibit HBV replication.

Hepatitis B virus (HBV) specific T cell immune response plays a vital role in viral clearance. Dendritic cell derived exosomes (Dexs) can activate T cell immunity effectively. Tapasin (TPN) is involved in antigen processing and specific immune recognition. In the present study, we elucidated that Dexs loading TPN (TPN-Dexs) could enhance CD8+ T cell immune response and inhibit virus replication in HBV transgenic mice. T cell immune response and the ability of inhibiting HBV replication were measured in HBV transgenic mice immunized with TPN-Dexs. Meanwhile, CD8+ T cell autophagy and specific T cell immune responses were measured in vitro and vivo, and the mechanisms probably involved in were explored. Purified TPN-Dexs could be taken up into the cytoplasm of DCs and upregulate CD8+ T cell autophagy to enhance specific T cell immune response. In addition, TPN-Dexs could increase the expression of AKT and decrease the expression of mTOR in CD8+ T cells. Further research confirmed that TPN-Dexs could inhibit virus replication and decrease the expression of HBsAg in the liver of HBV transgenic mice. Nevertheless, those also could elicit mice hepatocytes damage. In conclusion, TPN-Dexs could enhance specific CD8+ T cell immune responses via the AKT/mTOR pathway to regulate the autophagy and exert the antiviral effect in HBV transgenic mice.

USP9x promotes CD8 + T-cell dysfunction in association with autophagy inhibition in septic liver injury.

Sepsis is a life-threatening condition manifested by concurrent inflammation and immunosuppression. Ubiquitin-specific peptidase 9, X-linked (USP9x), is a USP domain-containing deubiquitinase which is required in T-cell development. In the present study, we investigate whether USP9x plays a role in hepatic CD8 + T-cell dysfunction in septic mice. We find that CD8 + T cells are decreased in the blood of septic patients with liver injury compared with those without liver injury, the CD4/CD8 ratio is increased, and the levels of cytolytic factors, granzyme B and perforin are downregulated. The number of hepatic CD8 + T cells and USP9x expression are both increased 24 h after cecal ligation and puncture-induced sepsis in a mouse model, a pattern similar to liver injury. The mechanism involves promotion of CD8 + T-cell dysfunction by USP9x associated with suppression of cell cytolytic activity via autophagy inhibition, which is reversed by the USP9x inhibitor WP1130. In the in vivo studies, autophagy is significantly increased in hepatic CD8 + T cells of septic mice with conditional knockout of mammalian target of rapamycin. This study shows that USP9x has the potential to be used as a therapeutic target in septic liver injury.

Collagen XV mediated the epithelial-mesenchymal transition to inhibit hepatocellular carcinoma metastasis.

Background: Hepatocellular carcinoma (HCC) is a malignant cancer with rapid progression, vascular invasion, a high recurrence rate and poor prognosis, so it is necessary to take early measures to halt this process. Accumulating evidence indicates that collagen XV (translated by Col15a1) is a basement membrane molecule related to tumour metastasis in several organs. However, the potential function of collagen XV in the liver associated with HCC remains to be further elucidated. Methods: Col15a1 was overexpressed in HepG2 and HCCLM3 cells. CCK8 and colony formation assays were used to assess the capacity of cell proliferation, and Transwell and wound healing assays were utilized to measure cell migration. Western blotting and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) quantified the protein and mRNA expression levels of genes related to the epithelial-mesenchymal transition (EMT). Then, the effect of collagen XV on tumour metastasis was confirmed in vivo. Finally, we inhibited discoidin domain receptor 1 (DDR1) via DDR1-IN-1 to explore whether the collagen XV interacted with DDR1 to regulate EMT. Results: Patients of HCC with higher expression of Col15a1 showed better survival than patients with low expression. Overexpression of collagen XV in HepG2 and HCCLM3 cells suppressed cell proliferation and migration in vitro and inhibited pulmonary and liver metastasis in vivo. In addition, collagen XV downregulated the DDR1 and transcription factor (Snail, Slug), regulated the EMT markers (Vimentin, E-cadherin, N-cadherin, and MMP9). Furthermore, inhibition of the DDR1 receptor by DDR1-IN-1 suppressed the gene promoting the EMT. Conclusions: Collagen XV functioned as a metastasis inhibitor in HCC by regulating the DDR1-Snail/Slug axis to regulate EMT.

Evaluation of the metagenomic next-generation sequencing performance in pathogenic detection in patients with spinal infection.

Spinal infection is a rarely occurred pathology, whose diagnosis remains a major challenge due to the low sensitivity of culturing techniques. Metagenomic next-generation sequencing (mNGS) is a novel approach to identify the pathogenic organisms in infectious diseases. In this study, mNGS technology was adopted for pathogenic detection in spinal infection from the tissue and pus samples. Additionally, the diagnostic performance of mNGS for spinal infection was evaluated, by comparing it with that of the conventional microbial culture, with the histopathological results as the gold standard. Overall, 56 samples from 38 patients were enrolled for mNGS testing, and 69 samples were included for microbial culture. 30 patients (78.95%) were identified to be positive by the mNGS method, which was higher than that of microbial culture (17, 44.74%). The sensitivity and specificity of mNGS with pus samples were 84.2% and 100.0%, respectively, which outperformed those of microbial culture (42.1% and 100.0%). The pathogen identification results were applied to medication guidance, and all 38 patients experienced favorable outcomes at three months, followed-up post-treatment, without any adverse effects. These findings proved that mNGS was superior to microbial culture in pathogenic identification of the spinal infection, thereby showing great promise in guiding drug administration and improving clinical outcomes.

Role of Autophagy in the Ubiquitinated Hepatitis B Virus Core Antigen Enhancing Dendritic Cell Function.

Dendritic cells (DCs), as the most powerful antigen-presenting cells, play a key role in the adaptive immune response, while the defective function of DC is an important factor in immune tolerance to hepatitis B virus (HBV) infection. Hepatitis B virus core antigen (HBcAg) is a highly antigenic protein that can induce a strong antigen-specific immune response against HBV. In this study, we first constructed the ubiquitinated HBcAg gene (UbHBcAg), and then utilized a recombinant lentiviral vector UbHBcAg (LV-UbHBcAg) to explore the role of them in DC autophagy and function. Meanwhile, the effects of autophagy on DC functional activation were further analyzed. Finally, we investigated the underlying mechanism of autophagy induced by LV-UbHBcAg. Results showed that LV-UbHBcAg could promote autophagic progression in DCs, and the upregulated autophagy can further enhance DC functional maturation. In addition, p62 may serve as an important role in autophagy degradation. More importantly, the PI3K/Akt/mTOR signaling pathway was involved in the process of autophagy induced by LV-UbHBcAg. These findings suggest that LV-UbHBcAg can activate DC function by inducing autophagy, which may represent a promising strategy to treat chronic HBV infection.

Astragalus polysaccharide alleviated hepatocyte senescence via autophagy pathway.

Aging is characterized by inevitable organ function decline over time, with consequent body deterioration and increased susceptibility to death. Astragalus polysaccharide (APS) has been reported to have anti-oxidative, anti-apoptotic, and anti-inflammatory properties. We investigated the potential protective effects of APS on hydrogen peroxide (H2 O2 ) induced hepatocyte senescence and identified related mechanisms in L02, Huh7, and LM3 cell lines. Aged female C57BL/6 mice were given APS for 1 week by intraperitoneal injection, and APS provided the strongest protective effect against H2 O2 -induced damage at 100 µM. APS reduced the expression of cell senescence markers and alleviated pathological damage in aged mouse liver. APS treatment decreased oxidative stress, apoptosis, NOD-like receptor protein-3-mediated pyroptosis, and maintained mitochondrial homeostasis. Notably, the protective effect of APS was weakened in the presence of chloroquine. APS might enrich autophagy by activating AMP-activated protein kinase (AMPK) and inhibiting mammalian target of rapamycin (mTOR). In conclusion, APS reduced reactive oxygen species levels, inhibited apoptosis and pyroptosis, and promoted mitophagy via AMPK/mTOR pathway to alleviate hepatocyte senescence in vitro and in vivo.

Adenovirus vector encoding TPPII ignites HBV-specific CTL response by activating autophagy in CD8+ T cell.

Early studies have shown that autophagy and TPPII are associated with HBV infection. In this study, adenovirus vector containing TPPII was constructed to immunize HBV transgenic mice in vivo to explore the potential mechanism of autophagy and HBV infection. Our goal is to provide new ideas for immunotherapy of hepatitis B. First, adenovirus vector containing TPPII was constructed. Then, we used adenovirus to immunize HBV transgenic mice and ATG5 knockout HBV transgenic mice. The autophagy of CD8+ T cells was detected by transmission electron microscopy and immunofluorescence electron microscopy, Western blot was used to detect the expression of autophagy LC3 and BECN1, CTL reaction, HBV DNA and HBsAg in serum, HBsAg and HBcAg in liver tissues by immunohistochemistry, to further examine the possible mechanisms involved in autophagy. Adv-HBcAg-TPPII promotes autophagy of CD8+ T lymphocyte, activates CTL response, inhibits HBV DNA replication and HBsAg expression, and PI3K/ Akt /m TOR signalling pathway may be involved in autophagy. This study demonstrates that autophagy of CD8+ T cells was induced by Adv-HBcAg-TPPII and the molecular mechanism may be related to the PI3K/ Akt /m TOR signalling pathway, providing a possible theoretical basis for immunotherapy of hepatitis B.

Molecular epidemiology and clinical characteristics of hepatitis delta virus (HDV) infected patients with elevated transaminases in Shanghai, China.

BACKGROUND: Patients coinfected with HBV and hepatitis D virus (HDV) have a greater risk of HCC and cirrhosis. The current study was undertaken to assess HDV genotype distribution and determine clinical characteristics of hepatitis delta virus (HDV) among HBsAg positive individuals in Shanghai. METHOD: This retrospective study involved 225 serum samples from HBsAg positive hospitalized patients from October 2010 to April 2013. HDV-specific RT-nested PCR was used to amplify HDV RNA. HDV genotypes were characterized by Next-generation sequencing (NGS), followed by phylogenetic analyses. HDV/HBV co-infected patients and HBV mono-infected patients were compared clinically and virologically. RESULTS: Out of the 225 HBsAg-positive serum samples with elevated transaminases, HDV-RNA was identified in 11 (4.9%) patients. The HBV loads in the HDV positive group were significantly lower than the HDV negative HBV-infected patients. The aminotransferase enzymes were significantly higher in HDV/HBV co-infected compared to HDV negative patients (P < 0.05). Phylogenetic analyses indicated that HDV-2 genotype being the predominant genotype, other HDV genotypes were not observed. HDV/HBV patients were significantly associated with a rather unfavourable clinical outcome. CONCLUSION: In summary, the prevalence of HDV infection in patients with elevated transaminases is not low and the predominance of HDV genotype 2 infection in Shanghai. This finding helps us to better understand the correlation of HDV/HBV co-infection. Moreover, Next-generation sequencing (NGS) technologies provide a rapid, precise method for generating HDV genomes to define infecting genotypes.

HOXA10 knockdown inhibits proliferation, induces cell cycle arrest and apoptosis in hepatocellular carcinoma cells through HDAC1.

BACKGROUND: Homeobox A10 (HOXA10) has been implicated in the development and progression of various human cancers. However, the precise biological functions of HOXA10 in hepatocellular carcinoma (HCC) have not been defined. METHODS: In this study, we examined mRNA expression by quantitative real-time PCR (qRT-PCR) of HOXA10 as well as histone deacetylase (HDAC) and protein levels by Western blot of HOXA10, HDAC1, Cyclin D1, proliferating cell nuclear antigen (PCNA), Survivin and p53 acetylation in HCC tissues and cell lines. We also assessed cell proliferation using Cell Counting Kit-8 (CCK-8) and analyzed cell cycle by flow cytometry. Furthermore, tumor growth of HCC cells in vivo was monitored using the nude mouse xenograft model. Finally, HDAC1 promoter activity and binding in HCC cell lines were detected by luciferase reporter assay and chromatin immunoprecipitation (ChIP), respectively. RESULTS: We uncovered the elevated expression of HOXA10 in HCC tissues compared to adjacent normal liver tissues. RNA interference-mediated knockdown of HOXA10 inhibited HCC cell proliferation both in vitro and in vivo. HOXA10 knockdown also induced cell cycle arrest at G0/G1 phase and apoptosis, which were accompanied with the reduced expression of Cyclin D1, PCNA and Survivin. Notably, HOXA10 knockdown enhanced p53 acetylation (Lys382), which is crucial to the activation of p53. Likewise, HOXA10 knockdown suppressed the transcription of HDAC1, a potential deacetylase for p53. In line with these observations, HDAC1 downregulation abrogated the effects of HOXA10 overexpression on proliferation, cell cycle progression, apoptosis and p53 acetylation, indicating the role of HDAC1 in mediating HOXA10 functions. CONCLUSION: Our results demonstrate that HOXA10 knockdown inhibits proliferation, induces cell cycle arrest and apoptosis in HCC cells by regulating HDAC1 transcription.

Plumbagin inhibits proliferation and induces apoptosis of hepatocellular carcinoma by downregulating the expression of SIVA.

Purpose: Plumbagin is thought to be a bioactive phytochemical drug and exerts an antitumor effect on various cancers. However, few studies focus on the antitumor activity of plumbagin on liver cancer. This study first investigated the antitumor activity of plumbagin on liver cancer and further investigated the molecular mechanism of its antitumor activity against hepatocellular carcinoma, both in vitro and in vivo. Methods: The antiproliferative activity of plumbagin was evaluated through CCK-8, EdU, and colony forming test. The cell cycle and apoptosis were then analyzed by flow cytometer. Western blot was used to detect the expression of apoptosis related protein, SIVA, and mTOR pathway. RNA-seq was performed to determine the gene expression profiles and overexpressed or knocked down SIVA to validate its role in plumbagin's antitumor activity. Regarding animal experiment, a xenograft model in BALB/c nude mice was built using LM3-Luci cells. Then bioluminescence imaging and further immunohistochemistry were performed to study the antitumor activity and the expression of SIVA and mTOR in the plumbagin-treated group. Results: Plumbagin can inhibit proliferation and induce apoptosis of liver cancer cells in vitro. Further experiment demonstrated that plumbagin could inhibit the expression of SIVA and subsequently downregulate the mTOR signaling pathway, and upregulating the expression of SIVA will alleviate the antitumor activity of plumbagin on liver cancer, which confirmed the important role of the SIVA/mTOR signaling pathway in the antitumor activity of plumbagin. In vivo bioluminescence imaging showed a decreased signal in the plumbagin-treated group, and further immunohistochemistry demonstrated that plumbagin could inhibit the SIVA/mTOR signaling pathway in tumor tissues. Conclusion: Our promising results showed that plumbagin could inhibit proliferation and induce apoptosis of hepatic cancer through inhibiting the SIVA/mTOR signaling pathway for the first time, which indicated that plumbagin might be a good candidate against liver cancer.

rhIL-1Ra reduces hepatocellular apoptosis in mice with acute liver failure mainly by inhibiting the activities of Kupffer cells.

In clinic, there is still no drug that can significantly improve the survival rate of patients with acute liver failure (ALF). We have confirmed that recombinant human IL-1 receptor antagonist (rhIL-1Ra) significantly improves the survival rate of acetaminophen (APAP)-induced ALF mice by reducing hepatocellular apoptosis. Here, we investigated the mechanism of this and the key target cells of rhIL-1Ra. In vivo, APAP-induced ALF mice were treated with rhIL-1Ra and gadolinium chloride (Gdcl3), respectively. Survival rates of mice, serum IL-1Ra and IL-1ß levels, IL-1 receptor type I (IL-1RI) and CD163 expression in the livers, and the phagocytic activities of Kupffer cells (KCs) were investigated. Additionally, the proliferation of hepatocytes and KCs in co-culture conditions with the serum of ALF mice were investigated in vitro. In this study, a large number of activated large KCs were found in liver lobe region III. Both GdCl3 and rhIL-1Ra significantly decreased the quantity of large KCs. In all of the mice, hepatocytes and liver non-parenchymal cells other than KCs expressed low levels of IL-1RI, whereas large KCs expressed high levels of IL-1RI. The high ratio of endogenous IL-1Ra/IL-1ß was related to rhIL-1Ra function. Additionally, the phagocytic activities of KCs were significantly inhibited by GdCl3 and rhIL-1Ra. In vitro, the proliferation of hepatocytes in co-culture conditions were significantly inhibited by KCs. In conclusion, large KCs were the key target cells of rhIL-1Ra, and rhIL-1Ra could play its role of reducing hepatocellular apoptosis mainly by inhibiting the activities of KCs.

Tripartite motif-containing protein 7 regulates hepatocellular carcinoma cell proliferation via the DUSP6/p38 pathway.

Tripartite motif-containing protein 7 (TRIM7), which is involved in the biosynthesis of glycogen, has been reported to drive lung tumorigenesis. In the present study, we aimed to examine the expression, roles and underlying molecular mechanisms of TRIM7 in hepatocellular carcinoma (HCC) development. Real-time PCR and immunohistochemical staining were performed to test the expression of TRIM7 in HCC tissues. Cell proliferation, cell cycle and tumorigenicity experiments were conducted to determine the function of TRIM7. The results showed that TRIM7 expression was elevated in human HCC tissues and that TRIM7 expression was significantly associated with tumor size, pTNM stage, serum α-fetoprotein (AFP) concentration, serum hepatitis B virus (HBV) DNA copy number and overall survival (OS) of HCC patients. TRIM7 knockdown inhibited the proliferation of HCC cells in vitro and in vivo. TRIM7 knockdown also induced a G1/S checkpoint in HCC cell lines. Additionally, TRIM7 knockdown led to decreased phosphorylated p38 (p-p38) and increased expression of p53 and p21. Ectopic expression of TRIM7 promoted HCC cell proliferation, cell cycle progression and p38 activation, but not in the presence of the p38 inhibitor SB203580. Moreover, TRIM7 overexpression enhanced the polyubiquitination and degradation of dual specificity phosphatase 6 (DUSP6). DUSP6 overexpression abolished the promotional effect of TRIM7 overexpression on HCC cell proliferation and the activation of p38. Furthermore, HBV X protein (HBx), a protein coded by HBV, was demonstrated to upregulate TRIM7 expression. Collectively, TRIM7 overexpression may contribute to the highly proliferative characteristics of HCC cells, and targeting TRIM7 might be a potential strategy for HCC treatment.

Immunization with lentiviral vector­modified dendritic cells encoding ubiquitinated hepatitis B core antigen promotes Th1 differentiation and antiviral immunity by enhancing p38 MAPK and JNK activation in HBV transgenic mice.

Hepatitis B virus (HBV) infection is a global public health problem. T helper (Th)1­associated cytokines are involved in HBV clearance during acute and persistent infection. In our previous study, it was demonstrated that lentiviral vectors encoding ubiquitinated hepatitis B core antigen (LV­Ub­HBcAg) effectively transduced dendritic cells (DCs) to induce maturation, which promoted T cell polarization to Th1 and generated HBcAg­specific cytotoxic T lymphocytes (CTLs) ex vivo. In the present study, HBV transgenic mice were immunized with LV­Ub­HBcAg­transduced DCs and HBcAg­specific immune responses were evaluated. Cytokine expression was analyzed by ELISA. T lymphocyte proliferation was detected with a Cell Counting Kit­8 assay and HBcAg­specific CTL activity was determined using a lactate dehydrogenase release assay. The expression levels of p38­mitogen­activated protein kinase (p38­MAPK), phosphorylated (p)­p38MAPK, c­Jun N­terminal kinase (JNK) and p­JNK were detected by western blot analysis. The results demonstrated that LV­Ub­HBcAg­transduced DCs significantly increased the Th1/Th2 cytokine ratio, and effectively reduced the levels of serum hepatitis B surface antigen (HBsAg), HBV DNA, and liver HBsAg and HBcAg. Furthermore, the LV­Ub­HBcAg­transduced DCs upregulated the expression of p­P38­MAPK and p­JNK in T lymphocytes. In conclusion, the present study indicated that LV­Ub­HBcAg­transduced DCs generated predominant Th1 responses and enhanced CTL activity in HBV transgenic mice. Activation of the P38­MAPK/JNK signaling pathway may be involved in this induction.

An engineered novel lentivector specifically transducing dendritic cells and eliciting robust HBV-specific CTL response by upregulating autophagy in T cells.

Dendritic cells (DCs) play a predominant role in initiating cell immune responses. Here we generated a DC-targeting lentiviral vector (LVDC-UbHBcAg-LIGHT) and evaluated its capacity to elicit HBV-specific cytotoxic T lymphocyte (CTL) responses. DC-SIGN-mediated specific transduction using this construct was confirmed in DC-SIGN-expressing 293T cells and ex vivo-cultured bone marrow cells. LVDC-UbHBcAg-LIGHT-loaded DCs were highly effective in inducing HBV-specific CTLs. Mechanistic studies demonstrated autophagy blocking led to a significant increase in apoptosis and obvious inhibition of CD8 + T cells entry into S-phase, correspondingly attenuated LVDC-UbHBcAg-LIGHT-loaded DC-induced T cell responses. This observation was supported by accumulation of pro-apoptotic proteins and the main negative cell cycle regulator-CDKN1B that otherwise would be degraded in activated T cells where autophagy preferentially occured. Our findings revealed an important role of autophagy in the activation of T cells and suggested LVDC-UbHBcAg-LIGHT may potentially be used as a therapeutic strategy to combat persistent HBV infection with higher security.

An Engineered DC-Targeting Lentivector Induces Robust T Cell Responses and Inhibits HBV Replication in HBV Transgenic Mice via Upregulating T Cell Autophagy.

BACKGROUND/AIMS: Developing engineered dendritic cell (DC)-targeting lentivectors (LVs) have been the target of intense research for their potential to create antigen-directed immunotherapeutics which can be safely administered to patients. In this study, we constructed a DC-directed LV (LVDC-UbHBcAg-LIGHT) as a potential vaccine to induce anti-HBV immune responses. METHODS: Specificity of LVDC-UbHBcAg-LIGHT for DCs in vivo was confirmed through live animal imaging studies. The levels of cytokine production in T cells were assessed by flow cytometry. The HBcAg-specific cytotoxic T lymphocyte (CTL) responses and antibody responses induced by direct administration of the LVs were detected by LDH release assay and ELISA respectively. The levels of serum HBsAg and HBV DNA were evaluated by Abbott kits and quantitative PCR respectively. The expression levels of HBsAg and HBcAg in liver tissues of HBV transgenic mice were examined by immunohistochemistry. In addition, molecular mechanism underlying the activation of CD8+ T cells was explored. RESULTS: Live animal imaging studies showed that following subcutaneous administration of LVDC-UbHBcAg-LIGHT, no obvious luminescence signal was detected at the injection site. Immunization with LVDC-UbHBcAg-LIGHT elicited potent T cell responses in HBV transgenic mice evidenced by increased percentages of IFN-γ, TNF-α and GzmB producing CD8+ T cells as well as IFN-γ producing CD4+ T cells, improved HBcAg-specific CTL activities and antibody responses. Additionally, vaccination with LVDC-UbHBcAg-LIGHT efficiently reduced serum HBsAg, HBV DNA levels and the expression of HBsAg and HBcAg in liver tissues of HBV transgenic mice. More importantly, autophagy was induced in the activated CD8+ T cells, and the induced autophagy noticeably promoted the proliferation of T cells and decreased the frequencies of apoptotic CD8+ T cells by selectively degrading ubiquitinated apoptosis and cell cycle-associated protein aggregates. Futhermore, we confirmed the interaction between autophagosomes and ubiquitinated aggregates by confocal microscopy and immunoprecipitation analysis. CONCLUSIONS: These results demonstrated that LVDC-UbHBcAg-LIGHT provided a simple method of eliciting effective antiviral immune responses in HBV transgenic mice and might potentially be used as a therapeutic strategy to eradicate HBV with more safety and efficiency. Moreover, our results revealed a direct role of autophagy in promoting the survival and proliferation of activated CD8+ T cells.