通讯机构：
[Qu, Xiaowang] U;Univ South China, Peoples Hosp Chenzhou 1, Translat Med Inst, 102 Luojiajing, Chenzhou 423000, Hunan, Peoples R China.
关键词：
hepatitis B surface antigen;neutralizing antibody;hepatitis B surface antigen;hepatitis C antibody;neutralizing antibody;adult;antibody response;Article;cellular distribution;controlled study;female;flow cytometry;hepatitis B;hepatitis C;human;human cell;major clinical study;male;mixed infection;priority journal;Tfh cell;Th1 cell;Th2 cell;blood;comparative study;cytology;drug use;helper cell;Hepacivirus;hepatitis B;Hepatitis B virus;hepatitis C;immunology;middle aged;T lymphocyte subpopulation;virology;virus load;Adult;Antibodies, Neutralizing;Coinfection;Drug Users;Female;Hepacivirus;Hepatitis B;Hepatitis B Surface Antigens;Hepatitis B virus;Hepatitis C;Hepatitis C Antibodies;Humans;Male;Middle Aged;T-Lymphocyte Subsets;T-Lymphocytes, Helper-Inducer;Viral Load
摘要：
Hepatitis C virus (HCV) and hepatitis B virus (HBV) coinfection reciprocally influences viral replication and host defence responses. This study aimed to investigate the impact of HBV coinfection on circulating T follicular helper cell (cTfh) distribution and the HCV neutralizing antibody (nAb) response. HCV neutralizing antibody responses were measured in individuals with HCV monoinfection (n = 83) and HBV/HCV coinfection (n = 78) using the HCV pseudoparticle neutralization assay. The frequencies of cTfh cells and their subsets in HCV monoinfection (n = 34) and HBV/HCV coinfection (n = 30) were analysed by flow cytometry. The correlations of clinical parameters, cTfh cells and neutralizing antibody responses were analysed. Compared with HCV monoinfection, the HBV coinfection group showed significantly lower HCV neutralizing antibody responses (P < 0.001) and a decreased frequency of circulating Th1-like Tfh cells (Tfh1) (P = 0.004). In HCV monoinfection, the frequency of the Tfh1 subset was positively correlated with HCV neutralizing antibody responses (R = 0.378, P = 0.03), but this correlation was lost under HBV/HCV coinfection (R = 0.115, P = 0.551). In contrast, the frequency of circulating Th2-like Tfh cells (Tfh2) was negatively correlated with the HCV neutralizing antibody responses (R = 0.404, P = 0.003). Further analysis showed that HBV coinfection enhanced the Tfh2 subset composition within cTfh cells (P < 0.001), which was associated with serum HBsAg in HBV/HCV coinfection (R = 0.521, P = 0.003). As expected, HBsAg also exhibited an inverse association with HCV neutralizing antibody responses in HBV/HCV coinfection (R = 0.59, P < 0.001). In contrast to HCV monoinfection, HBV/HCV coinfection leads to altered cTfh cell distribution and impaired HCV neutralizing antibody responses, which are associated with HBsAg. These findings will be helpful for better understanding the immunopathogenesis of HBV/HCV coinfection.
通讯机构：
[Qu, Xiaowang] U;[Qu, Xiaowang] S;Univ South China, Peoples Hosp Chenzhou 1, Translat Med Inst, Chenzhou 423000, Hunan, Peoples R China.;Southern Med Univ, Affiliated Peoples Hosp Chenzhou 1, Chenzhou 423000, Hunan, Peoples R China.
摘要：
<jats:title>Abstract</jats:title><jats:p>Circulating T follicular helper (cTfh) cells have been identified as counterparts of germinal center Tfh (GC Tfh) cells in humans and can support T-dependent B cell maturation and antibody production <jats:italic>in vitro</jats:italic>. However, the role of cTfh cells in neutralizing antibody (nAb) responses in HCV infection remains unclear. Here, we characterized the phenotype and function of cTfh cells and demonstrated the associations of cTfh cells and their subsets with nAb responses in HCV infection. A total of 38 HCV-infected individuals and 28 healthy controls were enrolled from a pool of injection drug users. The frequency and function of blood Tfh cells were analyzed by flow cytometry. The titers and breadths of serum nAbs were measured using HCV pseudo-particle neutralization assays. Herein, we report several key observations. First, HCV infection skewed cTfh toward CXCR3<jats:sup>+</jats:sup> cTfh cell differentiation. Second, the frequency of CXCR3<jats:sup>+</jats:sup> cTfh cells positively correlated with HCV nAb titers and breadths. Third, CXCR3<jats:sup>+</jats:sup> cTfh cells showed higher expression of Tfh-associated molecules (PD-1, ICOS, IL-21, Bcl-6) compared with CXCR3<jats:sup>−</jats:sup> cTfh cells from individuals with HCV infection. Coculture of cTfh cells and autologous memory B cells <jats:italic>in vitro</jats:italic> indicated that CXCR3<jats:sup>+</jats:sup> cTfh cells show a superior ability to support HCV E2-specific B cell expansion compared with CXCR3<jats:sup>−</jats:sup> cTfh cells from individuals with HCV infection. HCV infection skews cTfh cells toward CXCR3-biased Tfh cell differentiation, which positively correlates with the magnitude and breadth of the HCV nAb response. It is our hope that these findings will provide insights for the rational design of a nAb-based HCV vaccine.</jats:p>
通讯机构：
[Wu, Yimou] U;[Wu, Yimou] H;Univ South China, Med Coll, Inst Pathogen Biol, Hunan Prov Key Lab Special Pathogens Prevent & Co, Hengyang, Peoples R China.;Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
关键词：
Bcl-2 family proteins;Chlamydia psittaci;IFN-gamma;apoptosis;persistent infection
摘要：
Chlamydia psittaci is an obligate intracellular pathogen that can cause zoonosis. Persistent C. psittaci infection can inhibit apoptosis in host cells, thus extending their survival and enabling them to complete their growth cycle. In this study, the antiapoptotic effects of persistent C. psittaci infection, induced by treatment with IFN-γ, were found to be associated with both the death receptor and the mitochondrial pathways of apoptosis. These effects were mediated by Bcl-2 family members, as evidenced by the decreased expression of proapoptotic proteins, such as tBid and Bim. Simultaneously, the antiapoptotic protein Mcl-1 was upregulated by persistent C. psittaci infection. Increased phosphorylation of ERK1/2 was observed; however, the expression of Bad, unlike that of other proapoptotic proteins, did not seem to be involved in this process. In summary, persistent chlamydial infection exerts antiapoptotic effects through both the death receptor and the mitochondrial pathways, in a process that is regulated by the ERK1/2 and apoptotic proteins of the Bcl-2 family.
摘要：
The obligate intracellular bacterium Chlamydia psittaci is the causative agent of psittacosis in birds and humans. The capability of this zoonotic pathogen to develop a persistent phase may serve a role in the chronicity of infections, in addition to the failure of antibiotic therapy or immunoprophylaxis. In the present study, a C. psittaci strain 6BC persistent infection cell model was induced using interferon (IFN)-γ, alterations in the infectivity and morphology of the pathogen were analyzed, and the transcript profile of seven selected genes was analyzed. Following treatment with IFN-γ, the infectivity of C. psittaci 6BC was decreased, the inclusion bodies appeared to be smaller, reticulate bodies were larger and the number of infectious elementary bodies was decreased compared with acute infection. In IFN-γ-induced persistently infected cells, the relative mRNA expression levels of the genes CPSIT-0208, CPSIT-0310, CPSIT-0846, CPSIT-0844 and CPSIT-0594 were upregulated at 2-48 h post-infection (p.i.). The genes CPSIT-0959 and CPSIT-0057 were downregulated at 2-36 h p.i. The results of the present study advanced the understanding of C. psittaci persistent infection and demonstrated a number of previously unknown alterations in chlamydial gene expression, which may provide novel targets to further analyze this particular host-pathogen interaction.
作者机构：
[Hao, Xinrui; Ou, Xiang; Tang, Yaling; Hu, Yanwei; Li, Xiaoxu; Tang, Chaoke; Cao, Dongli; Dai, Xiaoyan] Univ S China, Key Lab Atherosclerol Human Prov, Cardiovasc Res Inst, Hengyang 421001, Peoples R China.
通讯机构：
[Tang, Chaoke] U;Univ S China, Key Lab Atherosclerol Human Prov, Cardiovasc Res Inst, Hengyang 421001, Peoples R China.
关键词：
semicarbazide-sensitive amine oxidase;nuclear receptor;liver X receptor;T0901317;atherosclerosis
摘要：
Semicarbazide-sensitive amine oxidase (SSAO) catalyzes oxidative deamination of primary aromatic and aliphatic amines. Increased SSAO activity has been found in atherosclerosis and diabetes mellitus. We hypothesize that the anti-atherogenic effect of liver X receptors (LXRs) might be related to the inhibition of SSAO gene expression and its activity. In this study, we investigated the effect of LXRagonist T0901317 on SSAO gene expression and its activity in apolipoprotein E knockout (apoE−/−) mice. Male apoE−/− mice (8 weeks old) were randomly divided into four groups: basal control group; vehicle group; prevention group; and treatment group. SSAO gene expression was analyzed by real-time quantitative polymerase chain reaction and its activity was determined. The activity of superoxide dismutase and content of malondialdehyde in the aorta and liver were also determined. In T0901317-treated mice, SSAO gene expression was significantly decreased in the aorta, liver, small intestine, and brain. SSAO activities in serum and in these tissues were also inhibited. The amount of superoxide dismutase in the aorta and liver of the prevention group and treatment group was significantly higher compared with the vehicle group (P < 0.05). Malondialdehyde in the tissues of these two groups was significantly lower compared with the vehicle group (P < 0.05). Our results showed that T0901317 inhibits SSAO gene expression and its activity in atherogenic apoE−/− mice. The atheroprotective effect of LXR agonist T0901317 is related to the inhibition of SSAO gene expression and its activity.
