[Show abstract][Hide abstract] ABSTRACT: During early HIV-1 infection (EHI), the interaction between the immune response and the virus determines disease progression. Although CD1c + myeloid dendritic cells (mDCs) can trigger the immune response, the relationship between CD1c + mDC alteration and disease progression has not yet been defined.
EHI changes in CD1c + mDC counts, surface marker (CD40, CD86, CD83) expression, and IL-12 secretion were assessed by flow cytometry in 29 patients.
When compared with the normal controls, patients with EHI displayed significantly lower CD1c + mDC counts and IL-12 secretion and increased surface markers. CD1c + mDC counts were positively correlated with CD4+ T cell counts and inversely associated with viral loads. IL-12 secretion was only positively associated with CD4+ T cell counts. Rapid progressors had lower counts, CD86 expression, and IL-12 secretion of CD1c + mDCs comparing with typical progressors. Kaplan-Meier analysis and Cox regression models suggested patients with low CD1c + mDC counts (<10 cells/μL) had a 4-fold higher risk of rapid disease progression than those with high CD1c + mDC counts. However, no relationship was found between surface markers or IL-12 secretion and disease progression.
During EHI, patients with low CD1c + mDC counts were more likely to experience rapid disease progression than those with high CD1c + mDC counts.
Full-text · Article · Dec 2015 · BMC Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Human Immunodeficiency Virus Type 1 (HIV-1) causes chronic infection characterized by the depletion of CD4+ T lymphocytes and the development of AIDS (Acquired Immunodeficiency Syndrome). Current antiretroviral drugs inhibit viral spread, but they do not lead to a full immune recovery. Hematopoietic stem cells (HSCs) and multipotent hematopoietic progenitor cells (HPCs) give rise to all blood and immune cells, and in HIV infection, hematological abnormalities frequently occur in patients. Here we used bone marrow samples from HIV-1 infected people to study the relationship between the proliferation ability of HSCs/HPCs and peripheral CD4+ T lymphocytes. Three indexes were used to reflect the proliferation ability of HSCs and HPCs: 1) colony-forming units of bone marrow mononuclear cells (BMMCs); 2) amplification of CD34+ cells purified from BMMCs; 3) expression of HOXB4 and HOXA9 in CD34+ cells. We observed a direct correlation between peripheral number of CD4+ T lymphocytes and the HSCs/HPCs proliferation ability in our study. We also compared HIV-infected patients with or without antiretroviral therapy (ART). Our results demonstrated that after ART, CD4+ T cell recovery and HPCs proliferation ability are correlated. Our findings have implications in understanding whether bone marrow (BM)-derived HPCs can supplement for the loss of CD4+ T lymphocytes during HIV-1 infection. Copyright
No preview · Article · Nov 2015 · JAIDS Journal of Acquired Immune Deficiency Syndromes
[Show abstract][Hide abstract] ABSTRACT: Numerous anomalies in B-cell phenotypes and functions have been described in HIV-infected individuals. However, the actual relationship between B cells and disease progression remains unclear. In this study, we investigated B-cell counts/percentages during a 12-month infection period in HIV-infected individuals that eventually developed into typical progressors (TPs) or rapid progressors (RPs). We found, after 12 months of infection, the baseline B-cell counts/percentages correlated positively with CD4
T-cell counts (
) and negatively with HIV viral set points (
). Kaplan-Meier survival analysis showed that high baseline B-cell counts/percentages were associated with a slow CD4-cell decline. B-cell kinetics indicated the baseline B-cell counts/percentages could be factors distinguishing between TPs and RPs. The combination of the baseline B-cell counts and percentages was associated with rapid disease progression (a 80.7% predictive value as measured by the area under the curve). These results indicate that the baseline B-cell counts/percentages might be associated with HIV disease progression.
[Show abstract][Hide abstract] ABSTRACT: In HIV disease course, the decline of peripheral CD4 T-cell count correlates with rapid disease progression. The supply of peripheral naive T cells by the thymus requires precursor T-cell proliferation within the thymus. In the setting of HIV-1 infection, when both naive and memory T cells are progressively depleted, the contribution of thymic dysfunction in CD4 depletion needs to be studied. Previous research has shown that thymic function may also be impaired in HIV-1 infection. However, it is inconclusive regarding whether this impairment occurred at the early time or during the chronic phase. In addition, the relationship between thymic dysfunction and disease progression remains unknown. In this study, we examined the thymic function in 65 HIV-infected individuals. Among them, 17 were in acute phase, 15 were in early chronic phase, 15 were in chronic phase with no ART (antiretroviral therapy), and 18 were on ART. We also included 11 uninfected individuals as controls. We measured the peripheral blood levels of T-cell receptor rearrangement excision circles and PTK7 and CD31 expressions for the frequency of circulating recent thymic emigrants. We observed that the 2 indicators of thymic function, sj/β-TREC and PTK7, seemed to be lower in the chronic infection group than those in the acute and early chronic groups. Both indicators returned to the normal level after ART. However, after 1-year follow-up of patients with early HIV-1 infection, rapid progressors (n = 4) had lower PTK7 and CD31 expressions than chronic progressors (n = 6).
No preview · Article · Aug 2015 · JAIDS Journal of Acquired Immune Deficiency Syndromes
[Show abstract][Hide abstract] ABSTRACT: Aims: To evaluate the prevalence and associated factors of reduced bone mineral density (BMD) among antiretroviral therapy (ART) naive HIV-infected male patients in China. Methods: We compared BMD between HIV-infected male patients and healthy controls. Risk factors of reduced BMD were studied using multivariable linear regression. Results: Reduced BMD rate of chronic HIV infection patients was higher. HIV infection was independently associated with decreased BMD after adjusting for demographic factors. Older age, lower BMI and men who have sex with men (MSM) were revealed as the risk factors of lower BMD in HIV-infected male patients. Conclusion: Reduced BMD rate of HIV-infected patients was high. Policies are needed for prevention and treatment.
[Show abstract][Hide abstract] ABSTRACT: Co-signaling molecules have been demonstrated to regulate regulatory T cells' (Tregs) function during human immunodeficiency virus (HIV) infection. A recently reported co-signaling molecule called herpes virus entry mediator (HVEM), a member of the tumor necrosis factor receptor family, can both enhance and inhibit the immune response. HVEM was also reported to enhance the suppressive function of regulatory T cells in mice. However, it remains unknown whether HVEM can regulate Treg function in HIV-infected patients or whether HVEM affects HIV disease progression. In this study, we found that the blockage of the HVEM could weaken Tregs' suppressive activity to effector T cells (Teffs). HVEM expression is reduced during the asymptomatic phase of HIV infection and fairly predictive of the recovery of CD4+T-cells in response to highly active anti-retroviral therapy (HAART), more so than nadir CD4+T-cell count or viral load. Taken together, these findings demonstrate the importance of HVEM in relation to Treg function and HIV disease progression, which would have therapeutic implications and provide insight into the pathogenesis of acquired immune deficiency syndrome (AIDS).
No preview · Article · Apr 2015 · Current HIV research
[Show abstract][Hide abstract] ABSTRACT: Background
Human immunodeficiency virus (HIV)-positive cases associated with men who have sex with men (MSM) have rapidly increased over the past years. The objective of this study is to comprehensively evaluate the proportions, changing trends, and geographical distribution of MSM-associated HIV cases from Chinese voluntary blood donors by systematically reviewing the available literature.Study Design and Methods
Major English and Chinese research databases were searched for studies reporting study locations, study years, the number of HIV infections among blood donors, and the number of HIV-positive donations associated with MSM in China. The proportion estimates were calculated; subgroup analyses and test for time trend were performed using software of comprehensive meta-analysis.ResultsThirty-four studies met eligibility criteria. The pooled proportion of HIV-positive donations associated with MSM from 2001 to 2012 was 36.5% (95% confidence interval, 29.6%-44.1%). The epidemic was found to be more severe in northeast and north China compared to south China (59.6%; 55.0% vs. 3.8%, respectively). The proportion showed a significantly increasing trend over the study period (10.3% in 2001-2005; 38.6% in 2006-2009; and 47.6% in 2010-2012; trend test chi-square = 16.42, p < 0.001).Conclusion
The relatively high proportion of MSM- associated HIV-positive donors is of concern. Efficient and effective measures focused on public education and improving knowledge of blood safety are needed to prevent this at-risk population from seeking HIV testing through blood donation. It is also imperative to expand the scope of postdonation nucleic acid testing to shorten the window period to improve blood supply safety in China.
[Show abstract][Hide abstract] ABSTRACT: CD3(+)CD56(+) NKT-like cells are one of the critical effectors in the immune response to viral infection and tumors, but the functional features of NKT-like cells in HIV infection have been rarely reported. In this study, we observed and described the state of NKT-like cell functions in primary HIV-infected individuals (PHIs), chronic HIV-infected individuals (CHIs), long-term nonprogressors (LTNPs), and HIV-negative controls (NCs). The results showed that the percentage of IFN- γ (+)CD3(+)CD56(+) NKT-like cells was notably higher in LTNPs compared with CHIs, and the proportion of CD3(+)CD56(+) NKT-like cells with dual function (IFN- γ (+)CD107a(+) NKT-like cells) in LTNPs was also much higher than in CHIs. Additionally, the percentages of IFN- γ (+)CD107a(+) NKT-like cells negatively correlated with viral load. Taken together, our data demonstrated that good functions of CD3(+)CD56(+) NKT-like cells in LTNPs likely occurred as a protective mechanism that slows down HIV disease progression.
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis (TB) and HIV are two worldwide public health concerns. Co-infection of these two diseases has been considered to be a major obstacle for the global efforts in reaching the goals for the prevention of HIV and TB.
A comprehensive cross-sectional study was conducted to recruit TB patients in three provinces (Guangxi, Henan and Sichuan) of China between April 1 and September 30, 2010.
A total of 1,032 consenting TB patients attended this survey during the study period. Among the participants, 3.30% were HIV positive; about one quarter had opportunistic infections. Nearly half of the participants were 50 years or older, the majority were male and about one third were from minority ethnic groups. After adjusting for site, gender and areas of residence (using the partial/selective Model 1), former commercial plasma donors (adjusted OR [aOR] = 33.71) and injecting drug users(aOR = 15.86) were found to have significantly higher risk of being HIV-positivity. In addition, having extramarital sexual relationship (aOR = 307.16), being engaged in commercial sex (aOR = 252.37), suffering from opportunistic infections in the past six months (aOR = 2.79), losing 10% or more of the body weight in the past six months (aOR = 5.90) and having abnormal chest X-ray findings (aOR = 20.40) were all significantly associated with HIV seropositivity (each p<0.05).
HIV prevalence among TB patients was high in the study areas of China. To control the dual epidemic, intervention strategies targeting socio-demographic and behavioral factors associated with higher risk of TB-HIV co-infection are urgently called for.
[Show abstract][Hide abstract] ABSTRACT: Background:
The number of new HIV infections among MSM of China is rapidly increasing in recent years and behavioral interventions have had limited effectiveness. To control the HIV pandemic may lie in an HIV vaccine. This study examined the factors associated with willingness to participate (WTP) in HIV vaccine clinical trials among China MSM.
A cross-sectional survey was carried out among MSM from three cities in northeast China. Questionnaires pertaining to MSM risk behavior and WTP in HIV vaccine trials were administered through computer assisted self-interviewing (CASI).
A total of 626 MSM participated in this survey. 54.8% had occasional male partners and 52.2% always used condoms with male sex partners. HIV prevalence was 5.0%. 76.7% were WTP in a preventive HIV vaccine clinical trial. Results showed that HIV vaccination is a means of protection for spouses and family; family support to participate in vaccine trials and desire for economic incentives were significantly associated with WTP.
There was a high proportion of WTP in HIV vaccine trials among Chinese MSM. The high HIV prevalence and high proportion of risky sexual behavior indicate that Liaoning MSM are potential candidates for HIV vaccine trials.
[Show abstract][Hide abstract] ABSTRACT: Cerebral malaria (CM) is associated with excessive host proinflammatory responses and endothelial activation. The hematopoietic hormone erythropoietin (EPO) possesses neuroprotective functions in animal models of ischemic-hypoxic, traumatic and inflammatory injuries. In the Plasmodium berghei ANKA model of experimental CM (ECM), recombinant human EPO (rhEPO) has shown evident protection against ECM. To elucidate the mechanism of EPO in this ECM model, we investigated the effect of rhEPO on host cellular immune responses. We demonstrated that improved survival of mice with ECM after rhEPO treatment was associated with reduced endothelial activation and improved integrity of the blood-brain barrier. Our results revealed that rhEPO down-regulated the inflammatory responses by directly inhibiting the levels and functions of splenic dendritic cells. Conversely, rhEPO treatment led to significant expansion of regulatory T cells and increased production of the anti-inflammatory cytokine IL-10. The data presented here provide evidence on the direct effect of rhEPO on host cellular immunity during ECM.
No preview · Article · Oct 2013 · Infection and immunity
[Show abstract][Hide abstract] ABSTRACT: Natural killer (NK) cells are important effectors of the innate immune system that help control viral infections and tumorigenesis. However, the relationship between NK cell function and HIV disease progression remains poorly defined. In this study, we examined the function of NK cells in Chinese patients who were HIV-infected but treatment-naïve. These individuals include primary HIV-infected patients (PHIs), typical progressors (TPs), and long-term nonprogressors (LTNPs). We observed an increase of CD56(dim) NK cells in PHIs, but the production of interferon-gamma (IFN-γ) and CD107a expression in PHIs were not altered compared with normal control subjects (NCs). However, the NK cells from LTNPs exhibited increased activities in IFN-γ production, CD107a expression and granzyme B change after K562 stimulation compared with NCs. Furthermore, the percentage of IFN-γ(+)CD107a(-) NK cells in LTNPs was higher than that in TPs, PHIs and NCs; levels of IFN-γ production in LTNP NK cells exhibited an inverse correlation with viral loads. Similar correlations, however, were not observed in the PHI and TP groups. Taken together, these data demonstrate that enhanced NK cell function may contribute to the control of HIV infection, and increased IFN-γ secretion may be associated with delayed disease progression.
No preview · Article · Sep 2013 · Journal of Clinical Immunology
[Show abstract][Hide abstract] ABSTRACT: Natural killer (NK) cells have emerged as pivotal players in innate immunity, especially in the defense against viral infections and tumors. Killer immunoglobulin-like receptors (KIRs) an important recognition receptor expressed on the surface of NK cells regulate the inhibition and/or activation of NK cells after interacting with human leukocyte antigen (HLA) class I ligands. Various KIR genes might impact the prognosis of many different diseases. The implications of KIR-HLA interaction in HIV disease progression remains poorly understood.
Here, we studied KIR genotypes, mRNA levels, HLA genotypes, CD4 T cell counts and viral loads in our cohort of Human Immunodeficiency Virus (HIV) infected individuals, a group that includes HIV long-term nonprogressors (LTNPs) and typical progressors (TPs).
We found that the frequency of KIR3DS1/L1 heterozygotes with HLA-Bw4-80I gene was much higher in LTNPs than in TPs (P=0.001) and that the KIR3DL1 homozygotes without HLA-Bw4-80I gene had higher viral loads and lower CD4 T cell counts (P=0.014 and P=0.021, respectively). Our study also confirmed that homozygosity for the HLA-Bw6 allele was associated with rapid disease progression. In addition to the aforementioned results on the DNA level, we observed that higher level expression of KIR3DS1 mRNA was in LTNP group, and that higher level expression of KIR3DL1 mRNA was in TP group.
Our data suggest that different KIR-HLA genotypes and different levels of transcripts associate with HIV disease progression.
Full-text · Article · Aug 2013 · BMC Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: The aim of this study is to systematically review the published studies and summarize the estimates of HIV and syphilis prevalences among high school and college student MSM in China in order to provide information for conducting targeted interventions.
Pubmed, Chinese National Knowledge Infrastructure, Wanfang and Google Scholar databases were searched in January 2013 to identify relevant articles. Data of eligible citations were extracted by two reviewers. All analyses were performed using Comprehensive Meta-Analysis V2.0 and SPSS V17.0.
Twenty-four eligible studies (6 in English and 18 in Chinese), published between 2006 and 2012, with a total of 3083 student MSM participants, were included. The meta-analyses showed that the prevalences of HIV and syphilis among studied student MSM were 4.4% (95% CI: 3.0%, 6.4%) and 5.7% (95% CI: 4.8%, 6.7%), respectively. HIV prevalence increased over the study period (3.0% in 2003-2006; 4.5% in 2007-2008, and 6.8% in 2009-2010, trend test chi-square = 11.3, p = 0.001).
Student MSM have become high-risk populations for HIV infection in China. The high prevalence of syphilis and the increasing HIV prevalence trend indicate the potential for a more severe HIV epidemic. Comprehensive intervention strategies that address condom promotion, syphilis detection and treatment, and health education need to be tailored to this vulnerable population to prevent HIV and syphilis infections.
[Show abstract][Hide abstract] ABSTRACT: A high prevalence of HIV infection is present among men who have sex with men (MSM) in China, but many people living with HIV or AIDS (PLWHs) are unaware of their HIV infection status. Provider-initiated HIV testing and counseling (PITC) is a streamlined model that can significantly enhance HIV detection and detect infections earlier. However, PITC has not yet been widely applied, and no studies have been conducted on MSM's attitudes towards PITC in China. In this study, a total of 438 MSM were recruited in Shenyang city. A multivariate logistic regression model showed that certain conditions made MSM more accepting of PITC: those who had attended VCT (voluntary counseling and testing) more than three times (odds ratio [OR]: 2.95, 95% CI: 1.36-6.37), those who considered PITC beneficial for family and friends (OR: 1.91, 95% CI: 1.25-2.92), those who obtained HIV/AIDS knowledge from brochures (OR: 2.52, 95% CI: 1.64-3.87), those who obtained HIV/AIDS knowledge from the Internet (OR: 1.66, 95% CI: 1.07-2.58), and those who were highly aware of their own risk of being infected with HIV (OR: 2.84, 95% CI: 1.37-5.91). To improve acceptance of PITC among MSM in China, stronger efforts are needed to lower the psychosocial barriers to receiving PITC, to promote HIV/AIDS awareness, and to encourage the extension of HIV testing.
[Show abstract][Hide abstract] ABSTRACT: Background
Yunnan has the largest number of reported HIV/AIDS cases among all Chinese provinces, the reported prevalence of HIV among Yunnan men who have sex with men (MSM) passed 10%, while HIV incidence epidemic and molecular characteristics of new infected Yunnan MSM were not evaluated before.
An 18 months prospective followed up with a frequency of 3 month per visit were conducted among HIV seronegative MSM in Kunming cityduring 2009–2011. Interviewer-administrated questionnaires were carried out. Blood specimens were obtained to test for syphilis and HIV, in which HIV were evaluated by standard HIV enzyme immunoassay (EIA) and HIV nucleic acid amplification testing (NAAT). Near full-length regions of the HIV-1 were evaluated for subtyping, primary drug resistance mutations.
During the follow-up 70.1% of the recruited 378 MSM retained in the cohort. Eleven MSM seroconverted to HIV and fifteen MSM seroconverted to syphilis. The HIV incidence and syphilis incidence was 3.5 (95% CI 1.8-6.2) cases /100 person year(PY) and 5.3 (95% CI 3.0-8.7) cases/100 PY, respectively. Multivariate analysis showed that baseline syphilis infection (aHR, 17.7), occupation (students vs. others [aHR, 5.7], retirees vs. others [aHR, 4.1]), bleeding experience after receptive anal intercourse (aHR,7.6), and minority ethnic(vs. Han) [aHR, 5.7] were independent risk factors for HIV seroconversion(each P<0.05). Among the 7/11 successfully amplified near full-length sequences, 71.4% (5/7) were CRF01_AE, and 28.6% (2/7) were CRF07_BC. Two HIV transmission pairs were detected among seroconverted minority ethnic MSM.
HIV incidence was moderately high among Yunnan MSM. Yunnan province need to strengthen both HIV and syphilis screening among MSM population. Some subpopulations of MSM, such as students, retirees and minority ethnic groups require more HIV epidemic surveillance and strengthened behavior interventions. HIV subtypes and primary drug resistance should be continually monitored to track cross-group transmission of HIV strains.
Full-text · Article · Jan 2013 · BMC Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: During malaria infection, multiple pro-inflammatory mediators including IFN-γ, TNF and nitric oxide (NO) play a crucial role in the protection against the parasites. Modulation of host immunity is an important strategy to improve the outcome of malaria infection. Allicin is the major biologically active component of garlic and shows anti-microbial activity. Allicin is also active against protozoan parasites including Plasmodium, which is thought to be mediated by inhibiting cysteine proteases. In this study, the immunomodulatory activities of allicin were assessed during acute malaria infection using a rodent malaria model Plasmodium yoelii 17XL.
To determine whether allicin modulates host immune responses against malaria infection, mice were treated with allicin after infection with P. yoelii 17XL. Mortality was checked daily and parasitaemia was determined every other day. Pro-inflammatory mediators and IL-4 were quantified by ELISA, while NO level was determined by the Griess method. The populations of dendritic cells (DCs), macrophages, CD4+ T and regulatory T cells (Treg) were assessed by FACS.
Allicin reduced parasitaemia and prolonged survival of the host in a dose-dependent manner. This effect is at least partially due to improved host immune responses. Results showed that allicin treatment enhanced the production of pro-inflammatory mediators such as IFN-γ, TNF, IL-12p70 and NO. The absolute numbers of CD4+ T cells, DCs and macrophages were significantly higher in allicin-treated mice. In addition, allicin promoted the maturation of CD11c+ DCs, whereas it did not cause major changes in IL-4 and the level of anti-inflammatory cytokine IL-10.
Allicin could partially protect host against P. yoelii 17XL through enhancement of the host innate and adaptive immune responses.
[Show abstract][Hide abstract] ABSTRACT: Excessive production of proinflammatory cytokines, elicited mostly by Th1 cells, is an important cause of cerebral malaria (CM). Dendritic cells (DCs), a critical link between innate and adaptive immune responses, rely heavily on Toll-like receptor (TLR) signaling. Using C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) as an experimental CM model, we first confirmed that inhibition of TLR9 by suppressive oligodeoxynucleotides protected mice from CM. In addition to being a well-known antimalarial, chloroquine (CQ) has been used as an immunomodulator of endocytic TLRs because it inhibits endosomal acidification. We found that immediately before and shortly after infection by PbA, treatment with a single dose of 50 mg/kg of CQ protected mice from experimental CM. Both CQ treatments significantly inhibited expression of TLR9 and MHC-II on DCs, and reduced the number of myeloid and plasmatocytoid DCs at 3 and 5 days after infection. Consequently, activation of CD4+ T cells, especially the expansion of the Th1 subsets, was dramatically inhibited in CQ treated groups, which was accompanied by a remarkable decline in the production of Th1 type proinflammatory mediators IFN-γ, TNF-α, and nitric oxide. Taken together, these results corroborated the involvement of TLR9 in CM pathogenesis and suggest that interference with the activation of this receptor is a promising strategy to prevent deleterious inflammatory response mediating pathogenesis and severity of malaria.
No preview · Article · May 2012 · International immunopharmacology