Unknown,Transcriptomics,Genomics,Proteomics

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Probiotic and Prebiotic Supplementation of Antiretroviral Therapy Improves Gastrointestinal Immunity in SIV-infected Macaques

ABSTRACT: HIV infection results in damage to the gastrointestinal (GI) tract, microbial translocation and immune activation, which are not completely ameliorated with suppression of viremia by antiretroviral (ARV) therapy. Furthermore, increased morbidity and mortality of ARV-treated HIV-infected individuals is associated with these dysfunctions. Thus, in order to enhance GI tract immunity, we treated SIV-infected pigtail macaques with ARVs supplemented with probiotics and prebiotics or with ARVs alone. In the colon, this synbiotic treatment resulted in increased expression of genes associated with antigen presenting cells (APCs), increased frequency and functionality of APCs, enhanced reconstitution and functionality of CD4+ T-cells and reduced fibrosis of lymphoid follicles. Thus, supplementing ARV treatment with synbiotic treatment in HIV-infected individuals may improve GI tract immunity and thereby mitigate inflammatory sequelae, ultimately improving prognosis. CD45+ (clone MB4-6D6) leukocytes were sorted from thawed colon samples from 4 ARV + probiotics animals and 4 ARV alone animals

ORGANISM(S): Macaca nemestrina

SUBMITTER: Peter Wilkinson

PROVIDER: E-GEOD-42232 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Attenuated poxviruses are safe and capable to express foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the highly attenuated, host-range restricted poxvirus NYVAC: deletion of the viral gene encoding type-I interferon-binding protein and development of attenuated replication-competent NYVAC. We evaluated these newly generated NYVAC mutants, encoding HIV-1 env, gag, pol and nef, for their ability to stimulate HIV-specific CD8 T-cell responses from blood mononuclear cells of HIV-infected subjects. The new vectors were evaluated and compared to the parental NYVAC vector in dendritic cells (DCs), RNA expression arrays, HIV gag expression and direct and cross-presentation assays in vitro. Deletion of type-I interferon-binding protein enhanced expression of interferon and interferon-induced genes in DCs, and increased maturation of infected DCs. Restoration of replication competence induced activation of pathways involving antigen processing and presentation. Also, replication-competent NYVAC showed increased Gag expression in infected cells, permitting enhanced cross-presentation to HIV-specific CD8 T cells and proliferation of HIV-specific memory CD8 T-cells. The recombinant NYVAC combining both modifications induced interferon-induced genes and genes involved in antigen processing and presentation, as well as increased Gag expression. This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines. RNA expression obtained from DCs infected by NYVAC-C-dB19R and NYVAC-C-KC-dB19R compared to RNA expression obtained from DCs infected by NYVAC-C Supplementary file 'normalized_data_Human_V3_V2.txt' reports data for ILMN identifiers common to platforms HumanRef8V2 and HumanRef8V3.

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Probiotic and Prebiotic Supplementation of Antiretroviral Therapy Improves Gastrointestinal Immunity in SIV-infected Macaques

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