ABSTRACT
BACKGROUND@#T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines.@*METHODS@#Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose.@*RESULTS@#Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W.@*CONCLUSIONS@#TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.
Subject(s)
Humans , Antibodies, Viral , CD8-Positive T-Lymphocytes , COVID-19/complications , COVID-19 Vaccines/immunology , HIV Infections/complications , Receptors, Immunologic , SARS-CoV-2ABSTRACT
Objective:To investigate the changes in adaptive phenotypes of Yersinia pestis ( Yp) during successive passages in macrophages. Methods:A Yp strain of 201-MI was induced by 50 successive passages of Yp 201 strain in Raw264.7 cells. Phenotypic characteristics of 201 and 201-MI strains were compared by analyzing their survival rates in macrophages, growth curves, biofilm formation abilities, acid and hydrogen peroxide-stress tolerance, and virulence to mammal cells (Raw264.7 and HeLa cells) and mice. Results:Comparing with 201 strain, 201-MI strain showed various phenotypic changes, including higher survival rate in Raw264.7 cells, faster growth in iron-deficient medium, higher tolerance to acid and hydrogen peroxide, decreased biofilm formation ability, and less damages to Raw264.7 and HeLa cells. More-over, 201-MI strain showed decreased virulence to mice in both subcutaneous and intraperitoneal challenges. Preliminary comparative genomics analysis revealed some indel and nonsense mutations in 201-MI strain, which might account for its phenotype changes.Conclusions:After successive passages in macrophages, Yp showed some phenotypic changes, which might reflect its adaptive evolution under the pressure of macrophages. Detailed multi-omics analysis would be of great help to understand the underlying genetic mechanisms of these changes, and the related Yp-macrophage interaction processes as well.
ABSTRACT
Geotrichum candidum is a filamentous fungus mostly used in the dairy industry for cheese ripening and flavoring. The current study was designed to evaluate the potential probiotics effect of dietary supplementation of G. candidum on growth, digestive enzymes activities, gut microbiota and immune-related gene expression and disease resistance in Gibel carp CAS â ¢ (Carassius auratus gibelio) against A. hydrophila infections. For this purpose, 420 healthy fish (initial body weight: 7.09 ± 0.02g) were randomly divided into 7 feeding groups in triplicates of 20 fish in each tank. Seven isocaloric and isonitrogenous diets were prepared, supplemented with 6 different doses of G. candidum viz; C: 0, T1:106, T2:107, T3:108, T4:109, T5:1010, T6:1011 CFU/kg diet and fed to fish twice a day for 60 days. Results showed significantly higher weight gain (WG) and feed efficiency (FE) in groups fed 106 and 108 CFU/kg diet compared to the control (P < 0.05). All G. candidum fed groups showed higher intestinal α-amylase activity (P < 0.05) while no difference in lipase and trypsin activity compared to the control group. Before challenge test, gut microbial diversity analysis revealed relatively more abundance of bacteria belonging to phylum Proteobacteria, Actinobacteria, Firmicutes and Bacteriodetes in group fed G. candidum supplemented diet and higher percentage of pathogenic bacteria belonging to order Aeromonadales and Vibrionales in control post-challenge. After challenge test immune response expressed numerically higher survival rate (P > 0.05) and significantly higher (P < 0.05) Respiratory Burst Activity(RBA), Immunoglobulin M level (IgM), Aspartate Transaminase activity (AST) and improved (P > 0.05) lysozyme activity, and Alanine Transaminase activity (ALT) in groups fed 106 and 108 CFU/kg G. candidum supplemented diet. The expression of immune related gene (IL-I ß, TNF- α, HSP70 and TLR-2) in liver of the fish were significantly affected (P < 0.05) by supplementation of G. candidum post bacterial challenge. The results showed that G. candidum is a potential probiotic as it could improve feed utilization, immunity and cause no harmful effects on growth of gibel carp at higher supplementation levels. The productive results can be achieved by using the lower dose as 106-108 CFU/kg diet.
