Whole Blood Stimulation Assay as a Treatment Outcome Monitoring Tool for VL Patients in Ethiopia: A Pilot EvaluationRead the full article
Journal of Immunology Research provides a platform for scientists and clinicians working in different and diverse areas of immunology and therapy.
Chief Editor, Professor Holland, has a background focusing on researching the development of conjunctival fibrosis and the characterisation of immune responses to potential C. trachomatis vaccine candidates.
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Genome-Wide Profiling of Human Papillomavirus DNA Integration into Human Genome and Its Influence on PD-L1 Expression in Chinese Uygur Cervical Cancer Women
Background. The Uygur is the fifth most populous ethnic group in China. Compared to other Chinese population, cervical cancer in them had high incidence, and HPV infection also was particular. Their HPV integration situation has never been reported. We aimed to investigate the integration situation of 20 subtypes of HPV gene into host cell genome in Chinese Uygur cervical cancer patients; meanwhile, we explored the influence of gene integration on PD-L1 expression. Methods. 40 frozen Chinese Uygur cervical cancer specimens with positive HPV infection were obtained from the cancer prevention and treatment institute of Tumor Hospital Affiliated to Xinjiang Medical University. The integration situation of HPV gene into host cell genome was detected by Agilent SureSelect™ Target Enrichment Chip and Next-Generation Sequencing. The related genes were analyzed by GO functional annotation and KEGG pathway enrichment. The expression levels of PD-L1 in cancer cells were tested by immunohistochemical assay (IHC). Meanwhile, the relationship between PD-L1 levels in cancer cells and gene integration were analyzed. Results. The HPV multiple infection rate by HIVID was as high as 92.5%, much higher than 35.0% by the commercial kit (). There were 13423 integration events in 40 specimens, involving 6867 human genes. These integration events were distributed on all human chromosomes, and chromosome 19 had the excessive concentration phenomenon of integration events. There were some integration hotspots in human genome such as PPP1R37, HECW2, EMBP1, ANKRD50, SPTBN4, LINC00895, LYRM4-AS1, LINC00374, RBFOX1, CSMD1, CDH13, and KLHL4. Insertion breakpoints can be found in all gene regions of the HPV genome. The actual observation of the integration times of E1 and E6 was much higher than the expected value, while the actual observation times of E5 were much lower than the expected value. The result of GO functional analysis showed that binding molecular function and cellular process biological process were the main ways to influence the cell biological behavior of HPV gene integration. The enrichment pathway analysis of KEGG showed that pathways in cancer were the most important enrichment pathways involved in the genomic integration of HPV. The positive PD-L1 rate was 62.5%. Logistic regression analysis showed that 9p24.1 existing integration sites and the number of all gene integration were risk factors for PD-L1 expression (odds ratio 17.313 and 1.012; 95% confidence interval 1.691-177.213 and 1.001-1.023). Conclusions and Relevance. Most high-frequency sites of HPV integration in Chinese Uygur cervical cancer are related to cancer progression, and the gene integration hotspots may be potential HPV carcinogenic targets. The problem of multiple HPV infection in Chinese Uygur cervical cancer patients should be paid attention. L1 and E6 genes are inapposite as the target gene of commercial HPV type detection kit, because of high-frequency breakpoints in these genes. The gene integration especially the integration existing on 9p24.1 could affect the expression level of PD-L1.
The First Report of Immunoglobulin G, M, and A Concentrations in Serum of European Bison and Their Changes with Age
The age-specific reference values for immunoglobulin (Ig) serum concentrations in European bison (Bison bonasus) are lacking. Identification of immune alterations that accompany normal physiological aging will help assist in development of better monitoring health programs. In the present study, the age-associated changes in concentration of IgG, IgM, and IgA in serum of apparently healthy European bison of various ages were studied. The quantities of IgA, IgM, and IgG were measured by the use of a commercial ELISA kit. The serum samples originating from apparently healthy European bison () were divided into the following age categories: (1) <1 year of age; (2) animals between 1 and 3 years of age; and (3) animals which have reached sexual maturity: (3a) animals between 4 and 8 years of age, (3b) animals between 9 and 15 years of age, and (3c) years of age. IgG was found to be predominant Ig in the serum regardless of the age of the animals. The significant positive correlation between IgG absolute and relative concentration and the age of animals was found. The absolute concentration of IgM did not differ significantly during the lifespan; however, the negative correlation was observed between percentage of IgM and European bison’s age. IgA represented the least class of serum Ig. Total serum concentration of analyzed Ig also significantly increased with age. No gender-related differences were detected. Our findings represent a meaningful contribution to the studies on the immunity of European bison and effect of age on the immunoglobulin level. Our results would be useful for veterinarians and researchers in the studies with this animal’s species.
Rotavirus VP6 Adjuvant Effect on Norovirus GII.4 Virus-Like Particle Uptake and Presentation by Bone Marrow-Derived Dendritic Cells In Vitro and In Vivo
We have previously shown that rotavirus (RV) inner capsid protein VP6 has an adjuvant effect on norovirus (NoV) virus-like particle- (VLP-) induced immune responses and studied the adjuvant mechanism in immortalized cell lines used as antigen-presenting cells (APCs). Here, we investigated the uptake and presentation of RV VP6 and NoV GII.4 VLPs by primary bone marrow-derived dendritic cells (BMDCs). The adjuvant effect of VP6 on GII.4 VLP presentation and NoV-specific immune response induction by BMDC in vivo was also studied. Intracellular staining demonstrated that BMDCs internalized both antigens, but VP6 more efficiently than NoV VLPs. Both antigens were processed and presented to antigen-primed T cells, which responded by robust interferon γ secretion. When GII.4 VLPs and VP6 were mixed in the same pulsing reaction, a subpopulation of the cells had uptaken both antigens. Furthermore, VP6 copulsing increased GII.4 VLP uptake by 37% and activated BMDCs to secrete 2-5-fold increased levels of interleukin 6 and tumor necrosis factor α compared to VLP pulsing alone. When in vitro-pulsed BMDCs were transferred to syngeneic BALB/c mice, VP6 improved NoV-specific antibody responses. The results of this study support the earlier findings of VP6 adjuvant effect in vitro and in vivo.
RNA N6-Methyladenosine Modifications and the Immune Response
N6-methyladenosine (m6A) is the most important modification of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) in higher eukaryotes. Modulation of m6A modifications relies on methyltransferases and demethylases. The discovery of binding proteins confirms that the m6A modification has a wide range of biological effects and significance at the molecular, cellular, and physiological levels. In recent years, techniques for investigating m6A modifications of RNA have developed rapidly. This article reviews the biological significance of RNA m6A modifications in the innate immune response, adaptive immune response, and viral infection.
Erythromycin Suppresses the Cigarette Smoke Extract-Exposed Dendritic Cell-Mediated Polarization of CD4+ T Cells into Th17 Cells
Cigarette smoke is a major effector of chronic obstructive pulmonary disease (COPD), and Th17 cells and dendritic cells (DCs) involve in the pathogenesis of COPD. Previous studies have demonstrated the anti-inflammatory effects of macrolides. However, the effects of macrolides on the cigarette smoke extract- (CSE-) induced immune response are unclear. Accordingly, in this study, we evaluated the effects of erythromycin (EM) on CSE-exposed DCs polarizing naïve CD4+ T cells into Th17 cells. DCs were generated from bone marrow-derived mononuclear cells isolated from male BALB/c mice and divided into five groups: control DC group, CSE-exposed DC group, CD40-antibody-blocked CSE-exposed DC group, and EM-treated CSE-exposed DC group. The function of polarizing CD4+ T cells into Th17 cells induced by all four groups of DCs was assayed based on the mixed lymphocyte reaction (MLR) of naïve CD4+ T cells. CD40 expression in DCs in the CSE-exposed group increased significantly compared with that in the control group (). The Th17 cells in the CSE-exposed DC/MLR group increased significantly compared with those in the control DC/MLR group (). Moreover, Th17 cells in the CD40-blocked CSE-exposed DC/MLR group and EM-treated CSE-exposed DC/MLR group were reduced compared with those in the CSE-exposed DC/MLR group (). Thus, these findings suggested that EM suppressed the CSE-exposed DC-mediated polarization of CD4+ T cells into Th17 cells and that this effect may be mediated through inhibition of the CD40/CD40L pathway.
Overview of Strategies to Improve Therapy against Tumors Using Natural Killer Cell
NK cells are lymphocytes with antitumor properties and can directly lyse tumor cells in a non-MHC-restricted manner. However, the tumor microenvironment affects the immune function of NK cells, which leads to immune evasion. This may be related to the pathogenesis of some diseases. Therefore, great efforts have been made to improve the immunotherapy effect of natural killer cells. NK cells from different sources can meet different clinical needs, in order to minimize the inhibition of NK cells and maximize the response potential of NK cells, for example, modification of NK cells can increase the number of NK cells in tumor target area, change the direction of NK cells, and improve their targeting ability to malignant cells. Checkpoint blocking is also a promising strategy for NK cells to kill tumor cells. Combination therapy is another strategy for improving antitumor ability, especially in combination with oncolytic viruses and nanomaterials. In this paper, the mechanisms affecting the activity of NK cells were reviewed, and the therapeutic potential of different basic NK cell strategies in tumor therapy was focused on. The main strategies for improving the immune function of NK cells were described, and some new strategies were proposed.