A Defect in Nucleosome Remodeling Prevents IL-12(p35) Gene Transcription in Neonatal Dendritic Cells

To gain insight into the inability of newborns to mount efficient Th1 responses, we analyzed the molecular basis of defective IL-12(p35) expression in human neonatal monocyte-derived dendritic cells (DCs). Determination of IL-12(p35) pre-mRNA levels by real-time RT-PCR revealed that transcriptional activation of the gene in lipopolysaccharide-stimulated neonatal DCs was strongly impaired compared with adult DCs. We next showed that p50/p65 and p65/p65 dimers interact with kB#1 site, a critical cis-acting element of the IL-12(p35) promoter. We found that LPS-induced p65 activation was similar in adult and newborn DCs. Likewise, in vitro binding activity to the Sp1#1 site, previously shown to be critical for IL-12(p35) gene activation, did not differ in adults and newborns. Since the accessibility to this Sp1#1 site was found to depend on nucleosome remodeling, we used a chromatin accessibility assay to compare remodeling of the relevant nucleosome (nuc-2) in adult and neonatal DCs. We observed that nuc-2 remodeling in neonatal DCs was profoundly impaired in response to lipopolysaccharide. Both nuc-2 remodeling and IL-12(p35) gene transcription were restored upon addition of recombinant interferon-γ. We conclude that IL-12(p35) transcriptional repression in neonatal DCs takes place at the chromatin level

Activation of natural killer cells and cytokine production in man by bacterial extracts

Broncho-Vaxon (OM-85 BV) is a bacterial extract of eight bacterias usually involved in the respiratory tract infections. Since Broncho-Vaxom is clinically active in decreasing the incidence of such infections, its immunological effect was investigated, in vitro, using peripheral blood mononuclear cells (PBMC). The experimental data indicate that Broncho-Vaxom can modulate various immune functions. It was shown, using a radioimmunoassay for these cytokines, that Broncho-Vaxom will spontaneously enhance TNFα and IL-2 production whereas it has no action on IFγ production. However, when the PBMC are stimulated with PHA, an increased production for IFγ, TNFα and IL-2 was observed suggesting that, under appropriate conditions, Broncho-Vaxom enhance the production of these cytokines. In other experiments, Broncho-Vaxom was shown to markedly increase the natural killer activity of PBMC. All these results demonstrate that Broncho-Vaxom is an immunomodulator affecting multiple immunological mechanisms including the activation of natural killer cells, of monocytes and of T cells through direct mechanisms or through the cytokine cascade.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Enhancement of cytokine production and natural killer activity by an Escherichia coli extract

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Activation of natural killer cells and cytokine production in humans by bacterial extracts (OM-85 BV)

The influence of Broncho-Vaxom (BV) on different immune parameters was investigated in vitro on human peripheral blood mononuclear cells (PBMC). It was found that BV enhances the natural killer (NK) activity of PBMC and increases their spontaneous and phytohemagglutin (PHA)-induced production of tumor-necrosis factor-α and interleukin-2 as well as the PHA-stimulated production of interferon-γ. These immunostimulating actions of BV on NK activity and cytokine production can contribute to the understanding of the enhancement of the body's defense mechanisms against respiratory tract infections.SCOPUS: cp.jinfo:eu-repo/semantics/publishe

Bacterial extract OM85-BV induces interleukin-12-dependent IFN-gamma production by human CD4+ T cells.

To obtain insight into the possible mode of action of bacterial extracts used as immunostimulants in Europe, we used the ELISPOT technique to investigate the effects of one of them (OM85-BV, Broncho-Vaxom) on interferon-y (IFN-gamma) production by peripheral blood mononuclear cells (PBMC). We found that (1) OM85-BV stimulates IFN-gamma secretion by PBMC from normal individuals and human immunodeficiency virus (HIV)-infected patients, (2) CD4+ cells represent the major source of IFN-gamma produced in response to OM85-BV, and (3) this effect of OM85-BV involves the induction of interleukin-12 (IL-12) secretion by accessory cells. We conclude that bacterial extracts might enhance antimicrobial defenses by eliciting IL-12-dependent IFN-gamma synthesis by CD4+ T cells.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Association de différents profils fonctionnels de cellules T spécifiques d’antigènes mycobactériens à la tuberculose active et latente.

info:eu-repo/semantics/nonPublishe

Differential antibody responses to Pneumococcal and Tetanus vaccines in asymptomatic HIV-infected patients :a serological and cellular study

info:eu-repo/semantics/nonPublishe

Specific memory B cells to 3 Bordetella pertussis antigens after cellular or acellular vaccine, or after whooping cough during childhood

info:eu-repo/semantics/nonPublishe

Different profiles of innate cells characterize active tuberculosis and latently infected subjects

info:eu-repo/semantics/nonPublishe