PubMed Health⌕ Search

Biomedical subjects

V Colizzi

Publications and source records attributed to V Colizzi.

At least 19 recordsLinked to original sources
PubMed2000

Human immunodeficiency virus type 1 infection modulates the interleukin (IL)-1beta and IL-6 responses of human macrophages to CD40 ligand stimulation.

Better understanding of the mechanisms of proinflammatory cytokine production during human immunodeficiency virus (HIV) type 1 infection is of pivotal importance. The effect of HIV-1 infection on recombinant CD40 ligand (CD40L)-induced interleukin (IL)-1beta and IL-6 production by human macrophages was analyzed. ELISA and cytofluorometric analysis demonstrated that CD40L stimulation of HIV-1-infected macrophages resulted in substantial production of IL-1beta and IL-6. In contrast, no cytokine response was observed in uninfected cells. No modulation of the receptor for CD40 was found to account for the enhanced response to CD40L. The CD40L effect was not due to lipopolysaccharide contamination and was completely abrogated by preincubation with a monoclonal anti-CD40L antibody. mRNA studies indicated that the priming effect of HIV-1 on the macrophage response to CD40L was regulated at the transcriptional level. Finally, the effect of HIV-1 on the cytokine response could not be abolished by the HIV-1 protease inhibitor U75875 at concentrations that completely suppressed HIV-1 replication.

Anti-HIV Agents↗
PubMed2000

Mycobacterium tuberculosis H37Rv comparative gene-expression analysis in synthetic medium and human macrophage.

Mycobacteria are intracellular pathogens that survive and grow in host macrophages. Following phagocytosis, sustained intracellular bacterial growth depends on its ability to avoid destruction by macrophage-mediated host defences such as lysosomal enzymes, reactive oxygen and the reactive nitrogen intermediates. This suggests that the interaction between host cell and microbe is delicately balanced, and can be tipped in favour of either organism. The identification of Mycobacterium tuberculosis H37Rv (MTB) genes expressed within host cells would contribute greatly to the development of new strategies to fight tuberculosis. In the present study, we compared MTB gene expression in the course of intra- (human macrophages) and extracellular growth (Sauton's medium) to ascertain whether differences might occur between gene-expression patterns in the two habitats of replication. Using reverse-transcriptase polymerase chain reaction (RT-PCR) on a group of 14 MTB-Complex-specific genes, we found that MT10Sa (a small stable RNA), 35 kDa (unknown), ahpC (alkyl hydroperoxide reductase, AhpC), sigF (alternative RNA Polymerase sigma factor), and katG (catalase-peroxidase, HPI) genes are expressed in both the environments, while Ag85B, Ag85C (members of the Antigen 85 Complex), rpoV (RNA Polymerase sigma factor) and ESAT6 (early secretory antigen, 6 kDa) are expressed only in the in vitro culture; on the other hand, Ag85A (Antigen 85 Complex), rpoB (RNA Polymerase beta sub-unit), pab (Protein antigen b), invA and invB genes (encoding proteins that show homologies with p60 of Listeria monocytogenes) are expressed only inside the macrophage. Positive RT-PCR products on cDNAs for these genomic regions were not obtained from approximately 1000-fold more bacteria grown in Laboratory Broth. Identification of M. tuberculosis genes expressed in response to phagocytosis by human macrophages increases our basic understanding of the host-pathogen interaction, and helps to identify bacterial factors necessary for in vivo survival and growth.

Colony Count, Microbial↗
PubMed2000

Mycobacterium tuberculosis-induced apoptosis in monocytes/macrophages: early membrane modifications and intracellular mycobacterial viability.

Apoptosis has been observed in monocytes/macrophages in the course of in vivo and in vitro Mycobacterium tuberculosis (MTB) infection. In order to define the early events of MTB-induced apoptosis, membrane CD14 expression and the exposure of Annexin V-binding sites in MTB-infected monocytes/macrophages have been monitored. Moreover, the role of MTB-induced apoptosis was further analyzed in vitro in terms of mycobacterial viability. Results show that monocyte/macrophage apoptosis is a very early event that is strictly dependent on the MTB amount, and this apoptosis is associated with a selective down-regulation of surface CD14 expression. Furthermore, no statistically significant decrease in mycobacterial viability was observed, which indicates that the apoptotic pathway triggered by high doses of MTB is associated with parasite survival rather than with killing of the parasite.

Apoptosis↗
PubMed2000

Decreased CD95 expression on naive T cells from HIV-infected persons undergoing highly active anti-retroviral therapy (HAART) and the influence of IL-2 low dose administration. Irhan Study Group.

The functional recovery of the immune system in HIV-infected persons receiving HAART and the role of adjuvant immune therapy are still matters of intensive investigation. We analysed the effects of HAART combined with cytokines in 22 naive asymptomatic individuals, randomized to receive HAART (n = 6), HAART plus a low dose (1000 000 U/daily) of rIL-2 (n = 8), and HAART plus rIL-2 after previous administration of granulocyte colony-stimulating factor (n = 8). After 3 months of therapy, increased CD4+ T cell counts and diminished viral loads were observed in all patients, independently of cytokine addition. A decreased expression of CD95 (Apo 1/Fas) was evident in all groups when compared with values before therapy. The percentages of peripheral blood mononuclear cells (PBMC) expressing CD95 after therapy decreased by 15%, 22% and 18% in the three treatment groups, respectively (P < 0.05). Analysis of PBMC subsets demonstrated that CD95 expression was significantly reduced on CD45RA+CD62L+ naive T cells (25.3%, 22.4%, and 18.6%, respectively; P < 0.05) in each group, after therapy. Accordingly, all patients showed a reduced rate of in vitro spontaneous apoptosis (P < 0.05). Another effect induced by HAART was a significant increase in IL-2Ralpha expression on total PBMC (P < 0.05), independently of cytokine addition. Altogether, our results suggest that very low dose administration of rIL-2 (1000 000 U/daily) may be not enough to induce a significant improvement in the immune system as regards HAART alone. The employment of higher doses of recombinant cytokines and/or different administration protocols in clinical trials might however contribute to ameliorate the immune reconstitution in patients undergoing HAART.

Adult↗
PubMed2000

gammadelta T-cell anergy in human immunodeficiency virus-infected persons with opportunistic infections and recovery after highly active antiretroviral therapy.

gammadelta T lymphocytes recognize non-peptidic microbial antigens without antigen processing and major histocompatibility complex (MHC) restriction, representing an early defence mechanism against invading pathogens. As a defective response to non-peptidic antigens was observed in human immunodeficiency virus-positive (HIV+) persons, the aims of this study were twofold: to analyse the incidence of gammadelta T-cell anergy in HIV+ positive patients with opportunistic infections/co-infections (HIV-OIC), and to investigate the role of highly active antiretroviral therapy (HAART) on gammadelta T-cell functions. Peripheral gammadelta T-cell distribution and in vitro reactivity to a non-peptidic mycobacterial antigen, isopentenyl pyrophosphate (IPP), were analysed. gammadelta T-cell subset distribution was altered more in HIV-OIC patients than in asymptomatic HIV+ subjects (HIV-ASY). Specifically, the Vdelta2/Vdelta1 ratio was inverted as a consequence of a decrease in Vdelta2 T-cell number. Moreover, IPP-stimulated Vdelta2 T cells from the HIV-OIC group displayed a major defect in interferon-gamma (IFN-gamma) production. Interestingly, HAART induced a sustained recovery of naive CD45RA+ and CD62L+ T cells and restored gammadelta T-cell function. Accordingly, in vitro CD45RA depletion resulted in gammadelta T-cell hyporesponsiveness. Altogether, the incidence of gammadelta T-cell anergy was increased in HIV-OIC patients and dependent on CD45RA helper function. Moreover, HAART was able to restore gammadelta T-cell reactivity, extending the immune recovery to non-peptide microbial antigens.

AIDS-Related Opportunistic Infections↗
PubMed1999

Expression of CCR5 is increased in human monocyte-derived macrophages and alveolar macrophages in the course of in vivo and in vitro Mycobacterium tuberculosis infection.

Human immunodeficiency virus (HIV) replicates more efficiently in Mycobacterium tuberculosis (MTB)-infected macrophages than in uninfected controls. We investigated whether this may be partly explained by changes in expression of CCR5 in the course of mycobacterial infection, as this molecule has been shown to be a coreceptor for HIV entry. Since the lung is the preferential organ of HIV replication in the course of tuberculosis, we preliminarily analyzed beta-chemokine receptor expression in alveolar macrophages from patients with active tuberculosis, using flow cytometry based on an MIP-1alpha ligand-biotin/avidin-FITC detection system. Increased MIP-1alpha receptor (MIP-1alphaR) expression in alveolar macrophages from infected patients was observed whereas no detectable expression could be revealed in uninfected controls. Since MIP-la can also bind CCR1 and CCR4, the presence of CCR5 mRNA was investigated in bronchoalveolar lavage (BAL) cells and detected in alveolar macrophages from tuberculosis patients only. The study was then extended to in vitro MTB-infected macrophages. Monocyte-derived macrophages (MDMs) were left to differentiate for 7 days before MTB H37Rv infection, and CCR5 expression was monitored, by using a specific monoclonal antibody, on days 1, 6, and 11 after infection. Increased CCR5 expression in MTB-infected macrophages was observed, with a peak on day 6 (64% in MTB-infected versus 33% in control cultures) and a decrease by day 11 (25% in MTB infected versus 13% in control cultures). These results show that CCR5 expression is enhanced in the course of in vitro MTB infection and during active pulmonary tuberculosis.

Cells, Cultured↗
PubMed1999

Nitric oxide inhibits the HIV-1 reverse transcriptase activity.

Nitric oxide (NO) is a polypotent regulatory molecule involved in a variety of activities, such as the modulation of the catalytic activity of cysteine-containing enzymes. The present study reports the modulation of the HIV-1 reverse transcriptase activity by NO, released by the NO-donors 3, 3-bis(aminoethyl)-1-hydroxy-2-oxo-1-triazene (NOC-18), (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR-3), 3-morpholinosydnonimine (SIN-1), 4-(phenylsulfonyl)-3-((2-(dimethylamino) ethyl)thio)furoxan oxalate (SNO-102), and sodium nitroprusside (SNP). NO inhibits dose-dependently the HIV-1 reverse transcriptase activity, likely due to oxidation of Cys residue(s). Present results, representing a new insight into the modulation mechanism of the HIV-1 reverse transcriptase activity, may be relevant to develop new strategies for inhibition of HIV-1 replication.

Catalysis↗
PubMed1999

Nitric oxide inhibits HIV-1 replication in human astrocytoma cells.

Astroglial cells represent a target for HIV infection in the central nervous system. In astrocytes, HIV infection is poorly productive, being characterized by a persistent state of viral latency. However, activation of the nuclear factor NF-kappaB and its binding to HIV long terminal repeat (LTR) can induce HIV replication. Moreover, nitric oxide (NO) can affect NF-kappaB activation in glial cells. Therefore, we hypothesize that NO may reduce HIV replication in human astroglial cells by inhibiting HIV-1 LTR transcriptional activity. In this respect, we show that NO donors reduce viral replication in HIV-1-infected human astrocytoma T67 cells, taken as an astroglial model. Furthermore, using transfected T67 cells, we demonstrate that NO donors inhibit HIV-1 LTR transcriptional activity. These results suggest that the use of NO-releasing drugs may represent a potential, novel approach in inhibiting HIV replication in the central nervous system.

Astrocytoma↗
PubMed1999

Tissue transglutaminase: apoptosis versus autoimmunity.

Autoimmune diseases are characterized by multiple autoantibodies and/or autoreactive T cells that recognize a large number of antigens. Many of these antigens undergo extensive post-translational modifications during apoptosis and act as substrates for the proapoptotic cystein proteases. Here, Mauro Piacentini and Vittorio Colizzi discuss the effects on autoimmunity produced by post-translational modifications of proteins catalysed by the proapoptotic enzyme tissue transglutaminase.

Animals↗
PubMed1999

The role of macrophage cell death in tuberculosis.

Studies of host responses to infection have traditionally focused on the direct antimicrobial activity of effector molecules (antibodies, complement, defensins, reactive oxygen and nitrogen intermediates) and immunocytes (macrophages, lymphocytes, and neutrophils among others). The discovery of the systems for programmed cell death of eukaryotic cells has revealed a unique role for this process in the complex interplay between microorganisms and their cellular targets or responding immunocytes. In particular, cells of the monocyte/macrophage lineage have been demonstrated to undergo apoptosis following intracellular infection with certain pathogens that are otherwise capable of surviving within the hostile environment of the phagosome or which can escape the phagosome. Mycobacterium tuberculosis is a prototypical 'intracellular parasite' of macrophages, and the direct induction of macrophage apoptosis by this organism has recently been reported from several laboratories. This paper reviews the current understanding of the mechanism and regulation of macrophage apoptosis in response to M. tuberculosis and examines the role this process plays in protective immunity and microbial virulence.

Animals↗
PubMed1999

Phosphoantigen-reactive Vgamma9Vdelta2 T lymphocytes suppress in vitro human immunodeficiency virus type 1 replication by cell-released antiviral factors including CC chemokines.

Vgamma9Vdelta2 T lymphocytes are broadly reactive against various intracellular pathogens and display both lytic and proliferative responses to human immunodeficiency virus (HIV)-infected cells. HIV infection of peripheral blood mononuclear cell cultures led to absolute increases in Vgamma9Vdelta2 T cells accompanied by decreased p24 levels. Strong gammadelta T cell activation with nonpeptidic mycobacterial phosphoantigens (TUBAg1 extract or synthetic isopentenyl pyrophosphate) resulted in potent inhibition of HIV replication through soluble released factors. Subsequent analyses showed that phosphoantigen-activated gammadelta T cells produced substantial amounts of beta-chemokines (macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, and regulated-on-activation, normal T-cell-expressed and -secreted beta-chemokine [RANTES]), which represent the natural ligand for the CCR5 HIV coreceptor. Accordingly, anti-beta-chemokine antibodies neutralized the inhibition of monocytotropic HIV strains by gammadelta T cell-released factors. Moreover, a T-tropic HIV strain using the CXCR4 coreceptor for virus entry was potently inhibited. Together, these data reveal that phosphoantigen-activated gammadelta T cells are an important source of CC chemokines and may suppress HIV replication through cell-released antiviral factors.

Antigens, Bacterial↗
PubMed1999

Molecular bases for the anti-HIV-1 effect of NO. Commentary.

In infected human cells, nitric oxide (NO) has been shown to inhibit the replication of the human immunodeficiency virus-1 (HIV-1), the etiological agent of AIDS. Evidence suggests that NO may regulate HIV-1 replication by affecting the sulphydryl redox state. In this respect, it has been very recently demonstrated that NO-donors inactivate the HIV-1-encoded protease and reverse transcriptase in vitro. Further viral and host NO targets may be envisaged. Although no data are available on the anti-HIV-1 effect of NO in vivo, NO-releasing drugs, clinically used in the treatment of cardiovascular disorders, may represent a novel class of molecules for decreasing virus replication. Here, the possible molecular bases for the anti-HIV-1 effect of NO are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1999

In vivo gammadelta T cell priming to mycobacterial antigens by primary Mycobacterium tuberculosis infection and exposure to nonpeptidic ligands.

BACKGROUND: The recognition of phosphorylated nonpeptidic microbial metabolites by Vgamma9Vdelta2 T cells does not appear to require the presence of MHC molecules or antigen processing, permitting rapid responses against microbial pathogens. These may constitute an important area of natural anti-infectious immunity. To provide evidence of their involvement in immune reactivities against mycobacteria, we measured the responsiveness of peripheral blood Vgamma9Vdelta2 T cells in children with primary Mycobacterium tuberculosis (MTB) infections. MATERIALS AND METHODS: Peripheral blood mononuclear cells from 22 children with MTB infections and 16 positivity of tuberculin (PPD)-negative healthy children were exposed to nonpeptidic antigens in vitro and the reactivity of the Vgamma9Vdelta2 T cell subset with these antigens was determined using proliferation and cytokine assays. Also, responses of gammadelta T cells from rhesus monkeys stimulated with phosphoantigens in vivo were measured. RESULTS: The Vgamma9Vdelta2 T cell responses were highly increased in infected children in comparison with age-matched controls. This augmented Vgamma9Vdelta2 T cell reactivity subsided after successful antibiotic chemotherapy, suggesting that persistent exposure to mycobacterial antigens is required for the maintenance of gammadelta T cell activation in vivo. The in vivo reactivity of Vgamma9Vdelta2 T cells to phosphoantigens was also analyzed in a rhesus monkey model system. Intravenous injections of phosphoantigens induced an activated state of simian Vgamma9Vdelta2 T cells which decreased after 2 months, i.e., with a time course similar to that seen in MTB-infected children. CONCLUSIONS: The increased reactivity of Vgamma9Vdelta2 T cells to phosphoantigens appears to be dependent on constant antigenic exposure. Consequently, the assessment of Vgamma9Vdelta2 responses may be useful for monitoring the efficacy of antimycobacterial therapies.

Animals↗
PubMed1998

Age-related propensity to peripheral expansion of Vgamma3+ gammadelta+ T lymphocytes after irradiation and bone marrow transplantation.

The age-related decline in T cell functions is generally considered to be due to changes in the responding alphabeta T cell populations as a result of impairment of T cell differentiation in the thymus. T cells bearing the gammadelta TCR are normally a minor subset of circulating T cells, but often the major T cell type among lymphocytes in epithelial tissues. In this paper we show that gammadelta T cells are expanded in lymph nodes of irradiated mice after syngenic bone marrow transplantation. Interestingly, these gammadelta T cells express mainly the Vgamma3 TCR, which is characteristic of dendritic epithelial T cells that can develop in athymic nude mice and may recognize self antigens. Since the peripheral expansion of Vgamma3 T lymphocytes is closely related to bone marrow age, these observations indicate that the age-related propensity to extrathymic development of Vgamma3+ gammadelta+ T lymphocytes is mainly due to stem cell dysregulation in aging. This phenomenon may contribute to T cell impairment and to the increased natural cytotoxic activity of lymphoid cells in aged mice.

Aging↗