Correlative factors of poor prognosis and abnormal cellular immune function in patients with Alzheimer’s disease

BACKGROUND Alzheimer’s disease(AD)is a serious disease causing human dementia and social problems.The quality of life and prognosis of AD patients have attracted much attention.The role of chronic immune inflammation in the pathogenesis of AD is becoming more and more important.AIM To study the relationship among cognitive dysfunction,abnormal cellular immune function,neuroimaging results and poor prognostic factors in patients.METHODS A retrospective analysis of 62 hospitalized patients clinical diagnosed with AD who were admitted to our hospital from November 2015 to November 2020.Collect cognitive dysfunction performance characteristics,laboratory test data and neuroimaging data from medical records within 24 h of admission,including Mini Mental State Examination Scale score,drawing clock test,blood T lymphocyte subsets,and neutrophils and lymphocyte ratio(NLR),disturbance of consciousness,extrapyramidal symptoms,electroencephalogram(EEG)and head nucleus magnetic spectroscopy(MRS)and other data.Multivariate logistic regression analysis was used to determine independent prog-nostic factors.the modified Rankin scale(mRS)was used to determine whether the prognosis was good.The correlation between drug treatment and prognostic mRS score was tested by the rank sum test.RESULTS Univariate analysis showed that abnormal cellular immune function,extrapyramidal symptoms,obvious disturbance of consciousness,abnormal EEG,increased NLR,abnormal MRS,and complicated pneumonia were related to the poor prognosis of AD patients.Multivariate logistic regression analysis showed that the decrease in the proportion of T lym-phocytes in the blood after abnormal cellular immune function(odd ratio:2.078,95%confidence interval:1.156-3.986,P<0.05)was an independent risk factor for predicting the poor prognosis of AD.The number of days of donepezil treatment to improve cognitive function was negatively correlated with mRS score(r=0.578,P<0.05).CONCLUSION The decrease in the proportion of T lymphocytes may have predictive value for the poor prognosis of AD.It is recommended that the proportion of T lymphocytes<55%is used as the cut-off threshold for predicting the poor prog-nosis of AD.The early and continuous drug treatment is associated with a good prognosis.

Dynamic changes of cellular immune function and individualized adjustments of immunosup-pressant for the management of severe infection after liver transplantation

Objective To explore the dynamic changes of the cellular immune function in severe infection after liver transplantation,and to guide the individualized immunology adjustment. Methods 378 cases of liver transplantation were analyzed retrospectively. Seventy - four cases ( infection group) suffered serious infection,including 54 cases cured ( cure group) ,20 cases died (

Efficient Humoral and Cellular Immune Responses Induced by a Chimeric Virus-like Particle Displaying the Epitope of EV71 without Adjuvant

Objective To eliminate the side effects of aluminum adjuvant and His-tag,we constructed chimeric VLPs displaying the epitope of EV71（SP70） without His-tagged.Then evaluating whether the VLPs could efficiently evoke not only humoral but also cellular immune responses against EV71 without adjuvant.Methods The fusion protein was constructed by inserting SP70 into the MIR of truncated HBc Ag sequence,expressed in E.Coli,and purified through ion exchange chromatography and density gradient centrifugation.Mice were immunized with the VLPs and sera were collected afterwards.The specific antibody titers,Ig G subtypes and neutralizing efficacy were detected by ELISA,neutralization assay,and EV71 lethal challenge.IFN-γ and IL-4 secreted by splenocytes were tested by ELISPOT assay.Results HBc-SP70 proteins can self-assemble into empty VLPs.After immunization with HBc-SP70 VLPs,the detectable anti-EV71 antibodies were effective in neutralizing EV71 and protected newborn mice from EV71 lethal challenge.There was no significant difference for the immune efficacy whether the aluminum adjuvant was added or not.The specific Ig G subtypes were mainly IgG1 and IgG2 b and splenocytes from the mice immunized produced high levels of IFN-γ and IL-4.Conclusion The fusion proteins without His-tagged was expressed and purified as soluble chimeric HBc-SP70 VLPs without renaturation.In the absence of adjuvant,they were efficient to elicit high levels of Th1/Th2 mixed immune response as well as assisted by aluminum adjuvant.Furthermore,the chimeric VLPs have potential to prevent HBV and EV71 infection simultaneously.

THE HUMORAL AND CELLULAR IMMUNE RESPONSES INDUCED BY HPV18L1-E6/E7 DNA VACCINES IN MICE

Objective To construct eukaryotic expression vector of HPV18 L1-E6, E7 chimeric gene and examine the humoral and cellular immune responses induced by this DNA vaccines in mice. Methods The C-terminal of major capsid protein L1 gene and mutant zinc finger domains of early E6/7 oncogenes in HPV18 were integrated and inserted into eukaryotic expression vector pVAX1 to generate vaccines pVAX1-L1E6Mxx, E7Mxx. CHO cells were transiently transfected with the individual construct. Target protein expressions in the lysate of the transfected cells were measured by ELISA and immunocytochemistry. After BALB/c mice were vaccinated with various recombinant plasmids(pVAX1-L1-E6M3 or pVAX1-L1-E7M3) and immunie adjuvants (pLXHDmB7-2 or LTB) through different administration routes (intramuscular or intranasal) , the great cellular immune responses were produced as revealed by delayed-type hypersensitivity (DTH) and lymphocyte proliferation, and the expression of IL-4 and IFN-γ cells in CD4 + and CD8 + subpopulations. Results The highly efficient expression of pVAX1-L1E6Mxx, E7Mxx vector in host eukaryotic cells were demonstrated both by ELISA and immunocytochemistry. The level of specific serum IgG against HPV in experiment groups mice was much higher than that of control group, and intranuscular immunization group had the highest antibody level. Intramuscular immunization groups were superior to intranasal immunization groups in DTH response, splenocyte proliferation and CD8+ IFN-γ + cells number, but CD4 + IL4 + cell number was higher in intranasal immunization groups. The immunization groups using pLXHDmB7-2 as adjuvant were superior to other groups in immunoresponse. Conclusion These DNA vaccines produce remarkable cellular and humoral immune responses in the mouse and may provide as prophylatic and therapeutic candidates for HPV induced cancer treatment.

The relationship between cellular immune level and diabetic foot in type 2 diabetic patients

Objective:To to investigate the correlation between the level of immune function and diabetic foot in type 2 diabetic patients.Methods:76 diabetic patients in our hospital from January 2017 to November 2019 were collected as the observation group(the observation group was divided into two subgroups:38 cases in DM group and 38 cases in DM+DF group)and 76 healthy people in the same period as the healthy control group.The level of cellular immunity in serum of the observation group and the healthy control group were compared,and the relationship between cellular immunity and diabetic foot was further explored Department.Results:there were significant differences in glycosylated hemoglobin and fasting blood glucose between the two groups(P<0.001);there were significant differences in CD8,CD25 and CD28 between the two groups(P<0.001).There were statistical differences in the course and age of diabetes between the two subgroups in the observation group(P<0.05);there were statistical differences in CD2,CD8,CD25 and CD28 between the two subgroups(P<0.05).Logistic regression analysis showed that CD8[or95%CI 0.920(0.850,0.995)]and CD25[or95%CI 0.764(0.619,0.943)]were independent influencing factors and risk factors of diabetic foot.Conclusion:the increased levels of CD8 and CD25 may increase the risk of diabetic foot.

Latent HIV-1 TAR Regulates 7SK-responsive P-TEFb Target Genes and Targets Cellular Immune Responses in the Absence of Tat

The transactivating response element （TAR） structure of the nascent HIV-1 transcript is critically involved in the recruitment of inactive positive transcription elongation factor b （P-TEFb） to the promoter proximal paused RNA polymerase II. The viral transactivator Tat is responsible for subsequent P-TEFb activation in order to start efficient viral transcription elongation. In the absence of the viral transactivator of transcription （Tat）, e.g., during latency or in early stages of HIV tran- scription, TAR mediates an interaction of P-TEFb with its inhibitor hexamethylene bis-aeetamide- inducible protein 1 （HEXIM1）, keeping P-TEFb in its inactive form. In this study, we address the function of HIV-1 TAR in the absence of Tat by analyzing consequences of HIV-1 TAR overexpres- sion on host cellular gene expression. An RNA chimera consisting of Epstein-Barr virus-expressed RNA 2 （EBER2） and HIV-1 TAR was developed to assure robust overexpression of TAR in HEK293 cells. The overexpression results in differential expression of more than 800 human genes. A significant proportion of these genes is involved in the suppression of cellular immune responses, including a significant set of 7SK-responsive P-TEFb target genes. Our findings identify a novel role for HIV-1 TAR in the absence of Tat, involving the interference with host cellular immune responses by targeting 7SK RNA-mediated gene expression and P-TEFb inactivation.

The humoral and cellular immune evasion of SARS-CoV-2 Omicron and sub-lineages

The recently discovered SARS-CoV-2 variant Omicron(B.1.1.529) has rapidly become a global public health issue.The substantial mutations in the spike protein in this new variant have raised concerns about its ability to escape from pre-existing immunity established by natural infection or vaccination. In this review, we give a summary of current knowledge concerning the antibody evasion properties of Omicron and its subvariants(BA.2, BA.2.12.1,BA.4/5, and BA.2.75) from therapeutic monoclonal antibodies and the sera of SARS-CoV-2 vaccine recipients or convalescent patients. We also summarize whether vaccine-induced cellular immunity(memory B cell and T cell response) can recognize Omicron specifically. In brief, the Omicron variants demonstrated remarkable antibody evasion, with even more striking antibody escape seen in the Omicron BA.4 and BA.5 sub-lineages. Luckily, the third booster vaccine dose significantly increased the neutralizing antibodies titers, and the vaccine-induced cellular response remains conserved and provides second-line defense against the Omicron.

Changes in cellular proliferation and plasma products are associated with liver failure

AIM To study the differences in immune response and cytokine profile between acute liver failure and selflimited acute hepatitis.METHODS Forty-six patients with self-limited acute hepatitis(AH), sixteen patients with acute liver failure(ALF), and twenty-two healthy subjects were involved in this study. The inflammatory and anti-inflammatory products in plasma samples were quantified using commercial enzyme-linked immunoassays and quantitative real-time PCR. The cellular immune responses were measured by proliferation assay using flow cytometry. The groups were divided into viral- and non-viral-induced selflimited AH and ALF. Thus, we worked with five groups: Hepatitis A virus(HAV)-induced self-limited acute hepatitis(HAV-AH), HAV-induced ALF(HAV-ALF), nonviral-induced self-limited acute hepatitis(non-viral AH), non-viral-induced acute liver failure(non-viral ALF), and healthy subjects(HC). Comparisons among HAV and non-viral-induced AH and ALF were performed.RESULTS The levels of mitochondrial DNA(mt DNA) and the cytokines investigated [interleukin(IL)-6, IL-8, IL-10, interferon gamma, and tumor necrosis factor] were significantly increased in ALF patients, independently of etiology(P < 0.05). High plasma mt DNA and IL-10 were the best markers associated with ALF [mt DNA: OR = 320.5(95%CI: 14.42-7123.33), P < 0.0001; and IL-10: OR = 18.8(95%CI: 1.38-257.94), P = 0.028] and death [mt DNA: OR = 12.1(95%CI: 2.57-57.07), P = 0.002; and IL-10: OR = 8.01(95%CI: 1.26-50.97), P = 0.027]. In the cellular proliferation assay, NK^(bright), NKT and regulatory T cells(TReg) predominated in virusspecific stimulation in HAV-induced ALF patients with an anergic behavior in the cellular response to mitotic stimulation. Therefore, in non-viral-induced ALF, anergic behavior of activated T cells was not observed after mitotic stimulation, as expected and as described by the literature. CONCLUSION mt DNA and IL-10 may be predictors of ALF and death. TReg cells are involved in immunological disturbance in HAV-induced ALF.

Immune Effects of Porcine Interleukin-2,4 on Piglets Using as Immunopotentiator for PCV Inactivated Vaccine

[ Objective] To investigate the combined immunization of porcine circovirus 2 （PCV2） inactivated vaccine with PoIL-2,4. [ Methods] A total of 60 crossbred piglets were randomly divided into three groups, including the test group （ inoculation of 0.5 dose PCV2 inactivated vaccine with 0. 1 mL PoIL-2,4 at 14 and 28 day-old）, the positive control group （inoculation of 0.5 dose PCV2 inactivated vaccine） and the blank control group. [ Results ] The immune organ index, the lymphocyte transformation rates under different ages and the number of leukocytes and lymphocytes in peripheral blood increased significantly in test group, compared with control group. Moreover, the antibody and neutralizing antibody were also significantly higher in test group than that in control group. The clinical symptoms and pathological changes were not found, and the PC72 was not detected in serum and tissue after challenge test in test group, which indicated that the combined immunization of PCV2 inactivated vaccine with PoIL-2,4 significantly improved the lymphocyte transformation rate, effectively prevented the replication of PCV2 in organism, and enhanced the growth performance of piglets.

Immunoregulatory Effects of Ethyl-acetate Fraction of Extracts from Tetrastigma Hemsleyanum Diels et. Gilg on Immune Functions of ICR Mice

Objective To evaluate the effects of ethyl-acetate fraction （EAF） of extracts from Tetrastigma hemsleyanum Diels et. Gilg （TDG） on immune functions of ICR mice. Methods ICR mice were exposed to different doses of EAF for 15 or 30 days and then their immune functions were analyzed, including ConA-induced splenic lymphocyte transformation, SRBC- induced delayed type hypersensitivity response, serum hemolysin analysis, antibody-producing cells, peritoneal macrophage phagocytized chicken red blood cells, natural killer cell activity, and serum level of cytoldnes. Results EAF of extracts from TDG at different doses had various effects on immune functions of ICR mice. As compared with the controls, it increased the mouse spleen lymphocyte transformation induced by ConA, the left-hind voix pedis thickness and the number of plague forming cells （PFCs） at the dose of 1.82 mg/mL, 5.48 mg/mL, and 9.12 mg/mL, respectively; increased the ink clearance ability at the dose of 0.91 mg/mL, 1.82 mg/mL, 5.48 mg/mL, and 9.12 mg/mL, respectively; increased the phagocytosis index of mononuclear-macrophages and production of serum interferon-gamma （IFN-？） at the dose of 5.48 mg/mL; and could promote the production of serum tumor necrosis factor-alpha （TNF-α） at the dose of 9.12 mg/mL. Conclusion EAF of extracts from TDG can regulate mouse immune functions in vivo.

Immune Responses to the Attenuated Mycoplasma hyopneumoniae 168 Strain Vaccine by Intrapulmonic Immunization in Piglets

To investigate the immune responses to the attenuated Mycoplasma hyopneumoniae 168 strain vaccine, 8-15 d old piglets were immunized with M. hyopneurnoniae 168 strain vaccine by intrapulmonic route. And the specific IgG antibody in serum, lymphoproliferation, IFNT, and specific secretory IgA （SIgA） antibody in bronchoalveolar lavage fluid were detected on 30 and 60 d post-immunization （DPI）, respectively. On 60 DPI, all the pigs except for those in health control group were challenged with a field M. hyopneumoniae strain JS. Necropsy was performed on 30 d post-challenge （DPC）. The results showed that IFN7 and specific SIgA were stimulated on surface of respiratory tract after immunization. And peripheral blood mononuclear cells could also be proliferated about 1.81 and 2.12 fold on 30 and 60 DPI when stimulated by M. hyopneumoniae protein in vitro. However, no serum IgG antibody against M. hyopneumoniae was detected during the whole immune phage. After challenge, vaccinated pigs were observed with only very slight histological lesion in individual lobes. None of vaccinated pigs showed any clinical signs. While the unvaccinated pigs from challenge control group showed varying degrees of clinical sign and severe macroscopical lesion of mycoplasmal pneumonia of swine （MPS）. The result suggested that the attenuated M. hyopneumoniae 168 strain vaccine inoculated by intrapulmonic route could activate the systemic cellular immunity, the local mucosal immunity and IFNγ secretion in respiratory tract to against M. hyopneumoniae infection in piglets.

Effect of Astragalus Injection on Serious Abdominal Traumatic Patients’ Cellular Immunity

Objective： To explore the change of serious abdominal traumatic patients＇ cellular immunity and the effect of Astragalus Injection （AI） on it. Methods： Sixty-three serious abdominal traumatic patients were randomly assigned into two groups, the conventional group and the treated group, patients in the conventional group were given conventional treatment, while others in the treated group were given conventional treatment as the basis, with Al20 ml was added into 250 ml of 5% glucose solution given through intravenous dripping, and then on the first day and 14th day, their T cell activated antigens as well as that of 10 healthy subjects were monitored. Results： On the first day, in the conventional group and treated group, the levels of CD3^＋ , CD4^＋ , CD4^＋/CD8^＋ , 0D16^＋ , CD69^＋ and CD3^＋/homologous leucocytic antigen-DR （HLA-DR＋ ） were apparently lower than those in the healthy group （ P〈0.05）, while the CD8^＋ was significantly higher than that in the healthy group （P〈0.05）, and there was no significant difference between the conventional group and the treated group （P〉0.05） ; on the 14th days, the levels of CD3^＋, CD4^＋, CD4^＋/CD8^＋, CD16^＋, CD69^＋ and CD3^＋/HLA-DR^＋ of the treated group got closed to healthy subject value, and got even higher than those of conventional group （P〈0. 05）; CD8^＋ got close to that of healthy subjects, while obviously lower than that of conventional group （ P〈0. 05）. Conclusion： After serious abdominal trauma, cellular immunity lowered, auxiliary use of AI was beneficial to the restoration of cellular immunity.

STUDY ON THE MECHANISM OF ESCAPING IMMUNE SURVEILLANCE IN HUMAN GLIOMAS

Objective: To study mechanisms by which human gliomas may escape immune surveillance Methods: The effect of supernatant (SN) obtained from cultured media of malignant glioma cell lines on the proliferation of phytohemagglutinin p stimulated peripheral blood lymphocytes (PBLs) from healthy subjects and patients with gliomas was examined by MTT assay The immunosuppressive factor which might be existed in the SN was identified by neutralization method with specific antibodies and Northern blot hybridization of glioma cells In addition, the cellular immunity of patients with gliomas and relevant hormone and catecholamine were determined Results: It was found that the malignant glioma cells could release an immunosuppressive factor in an autocrine fashion which was further identified as the transforming growth factor β 2 (TGF β 2) It was also demonstrated that the plasma levels of norepinephrine in glioma patients were significantly reduced and correlated well with the suppression of the patients' own cellular immunity Conclusions: Two distinct mechanisms by which human gliomas may evade immune surveillance: 1 The secretion of an immunosuppressive factor which was identified as TGF β 2; 2 The dysfunction of Neuro Immune modulation in the presence of cerebral gliomas

Impacts of Active Ingredients of Three Traditional Chinese Medicine on Immune Effect of PCV2 Vaccine

[ Objective ] The paper was to screen the active ingredients of traditional Chinese medicine （ TCM）, which significantly enhanced the immune effect of porcine circovirus type 2 （PCV2） vaccine. [Method]Sixty-six 14-day-old piglets were randomly divided into 11 groups, including immune control group, blank control group and nine drug groups. Piglets that were reared for 21 d were intramuscularly injected with 2 mL of inactivated vaccine in cervical region expect for blank control group. Piglets in nine drug groups were administrated with 5 mL of matrine, scutellarin and astragalus polysaecharide （ASP） at three doses （ high dose 12 mg, medium dose 8 nag, low dose 4 mg） three days before and after immunization; piglets in blank control group and irmnune control group were administrated with equal volume of normal saline. Five piglets were randomly selected from each group to collect venous blood at 7, 14, 21 and 28 d post immunization, and the PCV2 antibody level, the concentration of specific immunoglobulin [gG, the changes in peripheral blood lymphocyte subsets, and the content of serum IL-2 and IFN-γ were determined. [ Result] The immunological effects of active ingredients of three TCM on PCV2 vaccine all enhanced at different degree. The effects of scutellarin middle dose group was the best. [ Conclusion ] Scutellarin could be used as a candidate drug for PCV2 vaccine immunoenhancer.

Abnormalities of Cellular Immunoregulation in Patients with Epidemic Hemorrhagic Fever

In this report,a comparative study is made of the function test of spontaneousT suppressor cell（STs）and T Lymphocyte subsets in patients with epidemic hemorrha-gic fever（EHF）.It was found that in the early stages of the disease the activity of STs wasmarkedly lower than that of the controls,while the percentage of CD?+ cells increasedsignificantly,which led to the decrease and reciprocation of CD4/CD8 ratio,and that theactivity of STs was reversely related to the proportion of CD8+ cells on linear regressionanalysis,indicating that the CD8+ cells increased may mainly belong to cytotoxic T cells.It was also shown that the changes of STs function and CD4/CD8 ratio were related tothe abnormalities of serum C3 content and circulating immune complex.The results sug-gest that the disturbance of host cellular immunoregulation may play an important rolein the pathogenesis of EHF.

Live and Inactivated Salmonella Enteritidis Vaccines:Immune Mechanisms in Broiler Breeders

Salmonella is a ubiquitous pathogen which, in addition to causing poultry diseases, has a growing zoonotic impact. It has demanded the implementation of diverse control strategies, in which vaccines play a major role. The understanding of the immune pathways elicited by the different vaccines is important, contributing for the establishment of strong immune correlates of protection, for instance. With the purpose of determining the dynamics of the humoral and cellular immune responses to vaccination, broiler breeders (Cobb Slow) were immunized with live or inactivated vaccines against Salmonella Enteritidis. Lymphocyte and macrophage subsets were analyzed in the peripheral blood by flow cytometry and antigen-specific circulating IgY and mucosal IgA were quantified. The markers analyzed by flow cytometry were CD8/CD28, CD4/TCRVβ1, Kul/ MHC II and Bu-1. Both live and inactivated vaccines induced an increase in the proportion of circulating monocytes (Kul+MHCII+) in some time points compared to non-vaccinated controls. However, whereas the live vaccine leads to an increase in CD8-CD28+ and Bu-1+ lymphocytescompared to the control group, the inactivated vaccine prompteda reduction in the percentage of severalleucocyte subsets (Kul-MHCII+, Bu-1+, CD8+CD28+, CD8-CD28+, CD4+TCRVβ1-, CD4+TCRVβ1+, CD4-TCRVβ1+) after the boost dose. Both vaccines induced specific serum IgY and mucosal IgA production;however, the inactivated vaccine stimulated higher titers in a shorter period. These results contribute to the understanding of mechanisms of action of live and inactivated Salmonella vaccines in chickens.

Autologous bone marrow infusion via portal vein combined with splenectomy for decompensated liver cirrhosis: A retrospective study

BACKGROUND In a previous study,autologous bone marrow infusion(ABMI)was performed in patients with decompensated liver cirrhosis(DLC)and acquired immunodefi-ciency syndrome and achieved good results,but whether splenectomy affected outcome was unclear.AIM To investigate the efficacy of ABMI combined with splenectomy for treatment of DLC.METHODS Eighty-three patients with DLC were divided into an intervention group(43 cases)and control group(40 cases)according to whether splenectomy was performed.The control group was treated with ABMI through the right omental RESULTS After ABMI,the prothrombin time,serum total bilirubin levels,ascites volume and model for end-stage liver disease score in both groups were significantly lower,while the albumin levels were significantly higher than before ABMI(P<0.01),but there were no significant differences between the groups(P>0.05).After ABMI,the white blood cell and platelets counts in both groups were significantly higher than before ABMI(P<0.01),and the counts in the intervention group were significantly higher than in the control group(P<0.01).After ABMI the CD4+and CD8+T cell counts in both groups were significantly higher than before ABMI(P<0.01).The CD8+T cell counts in the intervention group increased continuously and the increase had a shorter duration compared with control group.CONCLUSION ABMI through the portal vein in patients with DLC can significantly improve liver synthetic and secretory functions,and splenectomy promotes improvement of bone marrow hematopoietic and cellular immune functions.

Silent battles:immune responses in asymptomatic SARS-CoV-2 infection

SARS-CoV-2 infections manifest with a broad spectrum of presentations,ranging from asymptomatic infections to severe pneumonia and fatal outcomes.This review centers on asymptomatic infections,a widely reported phenomenon that has substantially contributed to the rapid spread of the pandemic.In such asymptomatic infections,we focus on the role of innate,humoral,and cellular immunity.Notably,asymptomatic infections are characterized by an early and robust innate immune response,particularly a swift type 1 IFN reaction,alongside a rapid and broad induction of SARS-CoV-2-specific T cells.Often,antibody levels tend to be lower or undetectable after asymptomatic infections,suggesting that the rapid control of viral replication by innate and cellular responses might impede the full triggering of humoral immunity.Even if antibody levels are present in the early convalescent phase,they wane rapidly below serological detection limits,particularly following asymptomatic infection.Consequently,prevalence studies reliant solely on serological assays likely underestimate the extent of community exposure to the virus.

Rho 1 participates in parasitoid wasp eggs maturation and host cellular immunity inhibition

Endoparasitoid wasps introduce venom into their host insects during the egglaying stage.Venom proteins play various roles in the host physiology,development,immunity,and behavior manipulation and regulation.In this study,we identified a venom protein,MmRhol,a small guanine nucleotide-binding protein derived from ovary in the endoparasitoid wasp Microplitis mediator and found that knockdown of its expression by RNA interference caused down-regulation of vitellogenin and juvenile hormone,egg production,and cocoons formation in the female wasps.We demonstrated that MmRho1 entered the cotton bollworm's(host)hemocytes and suppressed cellular immune responses after parasitism using immunofluorescence staining.Furthermore,wasp MmRhol interacted with the cotton bollworm's actin cytoskeleton rearrangement regulator diaphanous by yeast 2-hybrid and glutathione s-transferase pull-down.In conclusion,this study indicates that MmRho1 plays dual roles in wasp development and the suppression of the host insect cellular immune responses.

Ampelopsin, a Small Molecule Inhibitor of HIV-1 Infection Targeting HIV Entry

Objective To investigate the anti-HIV effects of ampelopsin and its interaction with HIV-1 coreceptor CXCR4. Methods Through anti-virus experiments in vitro, the inhibitory effect of ampelopsin on HTV-1 infection was verified. Chemotaxis assay was performed to show the ability to induce PBMCs migration by ampelopsin, RANTES and SDF-la. Fluorescence labelling monoclonal antibody was utilized to observe the interaction of ampelopsin and CXCR4. Mice immunosuppressant model was also established to detail the role ampelopsin played in regulating cellular immunological functions. Results Ampelopsin could protect sensitive cells against HTV-1 infection and dramatically reduce HIV-1 antigen P24 expression. HTV-1SF33 attaching to MT-4 cells was interfered by ampelopsin, and the EC50 was 0.175 mg/mL for cellular protection and 0.024 mg/mL for P24 inhibition. At co-cultivating phase, EC50 was 0.229 mg/mL and 0.197 mg/mL respectively. Furthermore, the EC50 was 0.179 mg/mL and 0.348 mg/mL in acute infection. Human PBMCs migration was induced after being challenged with ampelopsin or chemokines, and synergistic action was observed during co-treatment. Ampelopsin alone resulted in maximal chemotaxis at 1 mg/mL. HIV-1 co-receptor CXCR4 on the surface of PBMCs was decreased by internalization, which indicated the effect of ampelopsin on CXCR4. About 70% CXCR4 was reduced by ampelopsin at 1 mg/mL. Ampelopsin also augmented cellular immunological functions in immunosuppressive mice. Conclusion Ampelopsin displays a strong inhibitive role during HIV-1 absorption, incubation and acute infection. These results are coincident with its immune enhancement.