20 research outputs found

    Triggering through NOD-2 differentiates bone marrow precursors to dendritic cells with potent bactericidal activity

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    Dendritic cells (DCs) play a crucial role in bridging innate and adaptive immunity by activating naĂŻve T cells. The role of pattern recognition receptors like Toll-Like Receptors and Nod-Like Receptors expressed on DCs is well-defined in the recognition of the pathogens. However, nothing is precisely studied regarding the impact of NOD-2 signaling during the differentiation of DCs. Consequently, we explored the role of NOD-2 signaling in the differentiation of DCs and therefore their capability to activate innate and adaptive immunity. Intriguingly, we observed that NOD-2 stimulated DCs (nDCs) acquired highly activated and matured phenotype and exhibited substantially greater bactericidal activity by robust production of nitric oxide. The mechanism involved in improving the functionality of nDCs was dependent on IFN-αÎČ signaling, leading to the activation of STAT pathways. Furthermore, we also observed that STAT-1 and STAT-4 dependent maturation and activation of DCs was under the feedback mechanism of SOCS-1 and SOCS-3 proteins. nDCs acquired enhanced potential to activate chiefly Th1 and Th17 immunity. Taken together, these results suggest that nDCs can be exploited as an immunotherapeutic agent in bolstering host immunity and imparting protection against the pathogens

    Signaling through NOD-2 and TLR-4 bolsters the T cell priming capability of dendritic cells by inducing autophagy

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    T cells play a cardinal role in mediating protection against intracellular pathogens like Mycobacterium tuberculosis (Mtb). It is important to understand the factors that govern the T cell response; thereby can modulate its activity. Dendritic cells (DCs) are the major player in initiation and augmentation of T cell response. Targeting DCs to induce their optimum maturation and activation can lead to a better T cell response. Interestingly, we observed that combinatorial signaling of DCs through NOD-2 and TLR-4 fortified better yield of IL-12p40/70, IL-6 and IFN-Îł and upregulated the expression of CD40, CD80 and CD86 costimulatory molecules. Further, we noticed improved phagocytic capabilities of DCs. Furthermore, NOD-2 and TLR-4 induced autophagy in DCs, which enhanced the activation of T cells. This study signifies that NOD-2 and TLR-4 exhibit synergism in invigorating the activity of DCs. Consequently, this strategy may have significant immunotherapeutic potential in bolstering the function of DCs and thus improving the immunity against pathogens

    TLR-3 Stimulation Skews M2 Macrophages to M1 Through IFN-αÎČ Signaling and Restricts Tumor Progression

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    During tumor progression, macrophages shift their protective M1-phenotype to pro-tumorigenic M2-subtype. Therefore, conversion of M2 to M1 phenotype may be a potential therapeutic intervention. TLRs are important pathogen recognition receptors expressed by cells of the immune system. Recently, a crucial role of TLR-3 has been suggested in cancer. Consequently, in the current study, we defined the role of TLR-3 in the reversion of M2-macrophages to M1. We analyzed the role of TLR-3 stimulation for skewing M2-macrophages to M1 at mRNA and protein level through qRT-PCR, flow cytometry, western blotting, and ELISA. The effectiveness of TLR-3L stimulation to revert M2-macrophages to M1 was evaluated in the murine tumor model. To determine the role of IFN-αÎČ signaling in vitro and in vivo, we used Ifnar1−/− macrophages and anti-IFN-αÎČ antibodies, respectively. We observed upregulation of M1-specific markers MHC-II and costimulatory molecules like CD86, CD80, and CD40 on M2-macrophages upon TLR-3 stimulation. In contrast, reduced expression of M2-indicators CD206, Tim-3, and pro-inflammatory cytokines was noticed. The administration of TLR-3L in the murine tumor reverted the M2-macrophages to M1-phenotype and regressed the tumor growth. The mechanism deciphered for macrophage reversion and controlling the tumor growth is dependent on IFN-αÎČ signaling pathway. The results indicate that the signaling through TLR-3 is important in protection against tumors by skewing M2-macrophages to protective M1-subtype

    Search for DCC in 158A GeV Pb+Pb Collisions

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    A detailed analysis of the phase space distributions of charged particles and photons have been carried out using two independent methods. The results indicate the presence of nonstatistical fluctuations in localized regions of phase space.Comment: Talk at the PANIC99 Conference, June 9-16, 199

    Present Status and Future of DCC Analysis

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    Disoriented Chiral Condensates (DCC) have been predicted to form in high energy heavy ion collisions where the approximate chiral symmetry of QCD has been restored. This leads to large imbalances in the production of charged to neutral pions. Sophisticated analysis methods are being developed to disentangle DCC events out of the large background of events with conventionally produced particles. We present a short review of current analysis methods and future prospects.Comment: 12 pages, 5 figures. Invited talk presented at the 13th International Conference on Ultrarelativistic Nucleus-Nucleus Collisions (Quark Matter 97), Tsukuba, Japan, 1-5 Dec 199

    Multiplicity Distributions and Charged-neutral Fluctuations

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    Results from the multiplicity distributions of inclusive photons and charged particles, scaling of particle multiplicities, event-by-event multiplicity fluctuations, and charged-neutral fluctuations in 158⋅A\cdot A GeV Pb+Pb collisions are presented and discussed. A scaling of charged particle multiplicity as Npart1.07±0.05N_{part}^{1.07\pm 0.05} and photons as Npart1.12±0.03N_{part}^{1.12\pm 0.03} have been observed, indicating violation of naive wounded nucleon model. The analysis of localized charged-neutral fluctuation indicates a model-independent demonstration of non-statistical fluctuations in both charged particles and photons in limited azimuthal regions. However, no correlated charged-neutral fluctuations are observed.Comment: Talk given at the International Symposium on Nuclear Physics (ISNP-2000), Mumbai, India, 18-22 Dec 2000, Proceedings to be published in Pramana, Journal of Physic

    Nanoparticles for hyperthermia applications

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    Cancer is one of the leading causes of death worldwide, and unfortunately many cancer treatments have severe side effects. In order to avoid these, recent investigations into new oncological treatments have been carried out. In this context, composite biomaterials have been developed mainly from biopolymers or magnetic hydroxyapatite nanoparticles with the aim of directing and releasing drugs by means of an external magnetic field (hyperthermia). This chapter reviews recent advances in nanoparticle (NP) systems for hyperthermia applications with particular emphasis on the heating mechanisms of iron NPs (INPs) and their applications as composite biomaterials.Fil: Gutiérrez Carmona, Tomy José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Alvarez, Vera Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentin

    Antibody response against PhoP efficiently discriminates among healthy individuals, tuberculosis patients and their contacts

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    <div><p>Tuberculosis continues to be one of the most devastating global health problem. Its diagnosis will benefit in timely initiation of the treatment, cure and therefore reduction in the transmission of the disease. Tests are available, but none can be comprehensively relied on for its diagnosis; especially in TB-endemic zones. PhoP is a key player in <i>Mycobacterium tuberculosis</i> virulence but nothing has been known about its role in the diagnosis of TB. We monitored the presence of anti-PhoP antibodies in the healthy, patients and their contacts. In addition, we also measured antibodies against early secretory antigens ESAT-6 and CFP-10, and latency associated antigen Acr-1 to include proteins that are associated with the different stages of disease progression. Healthy subjects showed high antibody titer against PhoP than patients and their contacts. In addition, a distinct pattern in the ratio of Acr-1/PhoP was observed among all cohorts. This study for the first time demonstrates a novel role of anti-PhoP antibodies, as a possible marker for the diagnosis of TB and therefore will contribute in the appropriate action and management of the disease.</p></div

    Ratio of Acr-1/PhoP antibody titer, discriminates among patients, contacts and healthy subjects.

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    <p>Antibodies ratio of (A) Acr-1/PhoP; (B) PhoP/Acr-1 were measured using the antibody titer against PhoP and Acr-1 in the serum of healthy, TB patients and close contacts. Median with 95% Cl represent the antibodies ratio between two antigens and each dot symbolizes single individual (N: number of individuals). *p<0.05, ****p<0.0001.</p

    PhoP showed maximum antibody titer compared to ESAT-6, CFP-10 and Acr-1.

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    <p>Antibodies against PhoP, Acr1, ESAT-6 and CFP-10 were measured in the serum of (A) patients; (B) contacts; (C) healthy. Median with 95% Cl represent the antibodies titers and each dot symbolizes single individual (N: number of individuals). **p<0.01, ***p<0.001, ****p<0.0001, ns: non-significant.</p