Fungal infection is an important clinical problem for patients with immune deficiency or immunosuppression. With deadly fungus infection case increasing, the development of antifungal vaccine attracts the attention of researchers. Dendritic cell (DC) is the unique antigen presenting cell (APC) to trigger the antifungal immune reaction, and recent studies indicate that the targeted vaccination strategy based on DC have prospective antifungal potentials. In this paper, we review the antifungal immunity mechanism and recent development of the targeted DC antifungal strategy.
Objective To observe the effect of transfer of immature mouse myeloid dendritic cells （DC） generated with low-dose granulocyte-macrophage colony-stimulating factor （GM-CSF） on cardiac allograft survival. Methods Mouse DC were generated with standard doses or low doses GM-CSF from bone marrow cells, the phenotype and functional properties of these DC were compared through fluorescence-activated cell sorting（FACS） analysis and mixed lymphocyte reaction（MLR）, 1. 0 × 106 DC generated with low doses GM-CSF were administered to the recipients 7 days before transplantation, and the cardiac allograft survival were observed. Results In contrast to DC generated with standard doses, DC generated with low doses were phenotypically immature DC （CD11c＋, CD80- , CD86- , MHCⅡlow）, and induced allogeneic T cell unresponsiveness, and administration of these DC to recipients prolonged cardiac allograft survival from 6.3±1.2 days to 14.3±1.9 days. Conclusions DC generated from mouse bone marrow progenitors in low doses of GM-CSF are phenotypically and functionally immature, and prolong cardiac allograft survival when they are administered 7 clays before transplantation.
Objective To explore the effect of dendritic cells (DCs) allergized by K-ras mutant peptide on expressions of chemokines CCL19, CCL22, and cytoskeletal protein fascin-1. Methods DCs were derived from peripheral blood in the presence of granuloceyte/macrophage-colony stimulating factor, interleukin (IL) -4 in vitro. The DCs were collected on day 7 after culture, and were divided into non-K-ras mutant peptide group (addition of RPMI 1604 culture solution 50 μg/ml) and K-ras mutant peptide group (addition of K-ras mutant peptide 50 μg/ml). Phenotype was identified by flow cytometry. The morphological structure was observed by scanning and transmission electron microscopies, respectively. The expressions of IL-12, CCL19, and CCL22 were tested continuously by enzyme-linked immunosorbent assay (ELISA). The expression of cytoskeletal protein fascin-1 was determined by Western blot. Results ①The expressions of CD1a, CD80, and CD86 after loading K-ras mutant peptide were higher than that before loading K-ras mutant peptide (Plt;0.01). ②The DCs with petal-like and branch-like profections after loading were observed under scanning electron microscopy; The DCs with irregular shapes, branch-like or burr-like were showed under transmission electron microscopy. ③The expressions of IL-12, CCL19, and CCL22 in the Kras mutant peptide group were higher than those in the non-K-ras mutant peptide group at different times (6, 12, 24, and 48 h) after loading Kras mutant peptide (Plt;0.01). ④The expression of fascin-1 in the K-ras mutant peptide group was also higher than that in the non-K-ras mutant peptide group (Plt;0.01). Conclusion K-ras mutant peptide can promote DC to mature and improve the expression of chemokines and cytoskeletal protein which will strengthen DC migration.
ObjectiveTo study the function of interleukin-10 (IL-10) in inhibiting the activation of dendritic cells (DC) in chronic severe hepatitis B patients. MethodsMonocytes were isolated from peripheral blood of 16 chronic severe hepatitis B patients between March and September 2012, by ficoll-hypaque density gradient centrifugation and then cultured with plastic-adherence method. Dendritic cells were induced and proliferated from the monocytes with granulocyte-macrophage colony stimulating factor and interleukin-4 for 8 days. Hepatitis B virus core antigen and IL-10 were used to the DC culture to treat DC. The expression of surface marker on dendritic cells was detected by fluorescence-activated cell sorter. The cytotoxic T lymphocyte activity, as well as the interferon (IFN)-γ, IL-12p70 secretion were observed. ResultsThe ratio of CD83, HLA-DR and CD86 positive cells, the concentration of IFN-γ and IL-12p70, as well as the cytotoxic T lymphocyte activity by dendritic cells were significantly increased in hepatitis B virus core antigen treated group and decreased in the IL-10 treated group compared with that in the control group. Meanwhile, the ratio of CD83, HLA-DR and CD86 positive cells, the concentration of IFN-γ and IL-12p70, as well as the cytotoxic T lymphocyte activity by dendritic cells were significantly decreased in IL-10 pretreated plus Hepatitis B virus core antigen treated group compared with that in the hepatitis B virus core antigen treated group. These results indicated that the hepatitis B virus core antigen could induce dendritic cells activation, and IL-10 could inhibit the activation of dendritic cells, even the Hepatitis B virus core antigen being added afterwards. ConclusionIL-10 can inhibit the activation of dendritic cells, and attenuate the cytotoxicity of autologous lymphocytes induced by DC.
Objective To investigate the expression of Bloom syndrome (BLM) helicase and tumor infiltrating dendritic cells (TIDC) in colon cancer tissues and their relationship with the prognosis of patients after surgery. Methods Onehundred and sixty-eight patients with colon cancer who underwent surgical resection in our hospital from June 2014 to August 2016 were selected as the research objects. The specimens of surgically resected colon cancer tissues and adjacent tissues archived by the pathology department were obtained, and the expression of BLM helicase and TIDC density were detected by immunohistochemistry. Pearson was used to analyze the correlation between BLM helicase expression and TIDC density, and the relationship between the expression of BLM helicase and TIDC density and the clinicopathological features of colon cancer was analyzed by using χ2 test or Wilcoxon rank test. The influencing factors of postoperative survival of patients with colon cancer were analyzed by Cox proportional hazards regression model. Results The relative expression of BLM helicase in colon cancer tissues was higher than that in adjacent tissues (1.49±0.33 vs. 1.02±0.17), while the TIDC density was lower than that in adjacent tissues [(9.53±2.36)% vs. (12.36±2.37)%], the differences were statistically significant (P<0.05). Pearson correlation analysis showed that there was a negative correlation between the expression of BLM helicase and TIDC density (r=–0.588, P<0.05). The expression of BLM helicase and TIDC density were correlated with tumor differentiation, clinical stage and lymph node metastasis (P<0.05). That is, those with high expression of BLM helicase and low density of TIDC had low degree of tumor differentiation, late clinical grade, and higher ratio of lymph node metastasis. Sixty-three cases died (37.5%) during the follow-up period (16–60 months, medium follow up 45 months). Log-rank analysis showed that the 5-year cumulative survival rate of the BLM helicase-low expression group was higher than that of the high expression group, and that of the TIDC-low density group was lower than that of the high density group (P<0.05). Cox regression analysis showed that the high expression of BLM helicase, low density of TIDC, low degree of tumor differentiation, late stage and lymph node metastasis were risk factors affecting the postoperative survival of patients with colon cancer (P<0.05). Conclusion The abnormal expression of BLM helicase and TIDC density in colon cancer tissues are related to the degree of differentiation and lymph node metastasis, which are risk factors affecting the long-term survival of patients with colon cancer.
Objective To study the mechanism of immune hyporesponsiveness of allograft rejection induced by transfusion nonpufsed allopeptide syngeneic immature dendritic cell (imDC) generated from recipient bone marrow progenitors and to explore a possible strategy for liver allograft protection in clinic. Methods Forty experimental rats were randomly divided into 4 group: control group, cyclosporine A (CsA) group, mature DC (mDC) group and imDC group. In control group, Wistar rats only received liver transplantation. In CsA group, Wistar rats underwent liver transplantation plus CsA treatment 〔10 mg/（kg·d)〕. In mDC group, recipient-derived mDC 1×106 were infused intravenously through the penile vein to Wistar rats. In imDC group, ImDC with the dose of 1×106 were injected into Wistar rats via the dorsum vein of penile. In each group, five recipients were killed on the 10th day after transplantation, the other five recipients were left to observe survival time. The levels of ALT, AST, TBIL, IL-2, IFN-γ, IL-4 and IL-10 were detected. The acute rejection and the expression of FasL/Fas in the grafts were detected by HE and immunohistochemical staining. Western blot was used to detect Scurfin protein expression of CD4+ CD25+ T cells. Results The median survival time of the liver allografts in CsA group and imDC group were significantly longer than that in control group and mDC group ( P ＜ 0.05). The levels of ALT and TBIL in control group and mDC group were significantly higher than those in CsA group and imDC group ( P ＜ 0.05). Compared with CsA group and imDC group, the levels of IL-2 and IFN-γ were higher but the levels of IL-4 and IL-10 were lower in control group and mDC group ( P ＜ 0.01). Slightly or no rejection reaction was found in CsA group and imDC group ( P ＜ 0.05). The Scurfin protein expressions of CD4+ CD25+ T cells of imDC group were significantly higher than those of other three groups. Conclusion Application of nonpufsed allopeptide syngeneic recipient-derived imDC is an effective way to induce immune hyporesponsiveness by blocking indirect recognition in rat liver transplantation model. Survival span is significantly prolonged by its protective effect. The mechanism of immune hyporesponsiveness induced by imDC transfusion might be involved in some aspects: T cell apoptosis, immune deviation of Thl/Th2 cytokine net and inhibition of T lymphocytes responsiveness by regulatory T cells.
Objective To investigate the effects of nuclear factor kappa B decoy oligodeoxynucleotides ( NF-κB decoy ODN) transfection on biological characteristics of mature dendritic cells ( mDCs) in mice. Methods Immature DCs were harvested from Balb / c mice bone marrow, followed by the incubation with antigen OVA and LPS, and mature DCs were evaluated by the expressions of CD11c and MHC-Ⅱ detected by FACS. Mature DCs were transfected with NF-κB decoy ODN and the changes of NF-κB activity after the transfection were detected by EMSA. The expressions of the costimulatory molecules( CD40,CD80 and CD86) on DCs were detected by FACS and the proliferation of T cells was tested by mixed lymphocyte reaction( MLR) . Results The mature DCs were cultured successfully. The NF-κB activity of NF-κB decoy ODN transfected DCs was decreased significantly( P lt; 0. 05) . There was no difference in the expressions of CD40 and CD80, but the expression of CD86 was decreased significantly in NF-κB decoy ODN transfection group( P lt; 0. 05) . MLR test showed that the proliferation of T lymphocyte cells was inhibited by NF-κB decoy ODN transfected DCs, but was stimulated bly by the DCs of other groups. Conclusions Mature DCs transfected with NF-κB decoy ODN could inhibit the proliferation and activation of antigenspecical T cells, which was probably related to the down-regulation of CD86 on DCs. This modified DCs might be a promising vaccine for the treatment of asthma in the future.