Evidence for interleukin-1-independent stimulation of interleukin-12 and down-regulation by interleukin-10 inHelicobacter pylori-infected murine dendritic cells deficient in the interleukin-1 receptor

ABSTRACT The Mycobacterium tuberculosis genome encodes 13 sigma factors. We have previously shown that mutations in some of these transcriptional activators render M. tuberculosis sensitive to various environmental stresses and can attenuate the virulence phenotype. In this work, we focused on extracytoplasmic factor σE and studied the effects induced by the deletion of its structural gene (sigE) in the infection of human monocyte-derived dendritic cells (MDDC). We found that the wild-type M. tuberculosis strain (H37Rv), the sigE mutant (ST28), and the complemented strain (ST29) were able to infect dendritic cells (DC) to similar extents, although at 4 days postinfection a reduced ability to grow inside MDDC was observed for the sigE mutant ST28. After mycobacterium capture, the majority of MDDC underwent full maturation and expressed both inflammatory cytokines, such as tumor necrosis factor alpha, and the regulatory cytokines interleukin-12 (IL-12), IL-18, and beta interferon (IFN-β). Conversely, a higher level of production of IL-10 was observed in ST28-infected MDDC compared to H37Rv- or ST29-infected cell results. However, in spite of the presence of IL-10, supernatants from ST28-infected DC induced IFN-γ production by T cells similarly to those from H37Rv-infected DC culture. On the other hand, IL-10 impaired CXCL10 production in sigE mutant-infected DC and, indeed, its neutralization restored CXCL10 secretion. In line with these results, supernatants from ST28-infected cells showed a decreased capability to recruit CXCR3+ CD4+ T cells compared to those obtained from H37Rv-infected DC culture. Thus, our findings suggest that the sigE mutant-induced secretion of IL-10 inhibits CXCL10 expression and, in turn, the recruitment of activated-effector cells involved in the formation of granulomas.

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Regulation of IL-10 and IL-12 production and function in macrophages and dendritic cells

F1000Research ◽

10.12688/f1000research.7010.1 ◽

2015 ◽

Vol 4 ◽

pp. 1465 ◽

Cited By ~ 76

Author(s):

Xiaojing Ma ◽

Wenjun Yan ◽

Hua Zheng ◽

Qinglin Du ◽

Lixing Zhang ◽

...

Keyword(s):

Dendritic Cells ◽

Clinical Intervention ◽

Interleukin 10 ◽

Intervention Strategies ◽

Interleukin 12 ◽

Signaling Mechanisms ◽

Wide Range ◽

Human Disorders ◽

And Function ◽

Antigen Presenting

Interleukin-10 and Interleukin-12 are produced primarily by pathogen-activated antigen-presenting cells, particularly macrophages and dendritic cells. IL-10 and IL-12 play very important immunoregulatory roles in host defense and immune homeostasis. Being anti- and pro-inflammatory in nature, respectively, their functions are antagonistically opposing. A comprehensive and in-depth understanding of their immunological properties and signaling mechanisms will help develop better clinical intervention strategies in therapy for a wide range of human disorders. Here, we provide an update on some emerging concepts, controversies, unanswered questions, and opinions regarding the immune signaling of IL-10 and IL-12.

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CD40-deficient dendritic cells producing interleukin-10, but not interleukin-12, induce T-cell hyporesponsiveness in vitro and prevent acute allograft rejection

Immunology ◽

10.1046/j.1365-2567.1999.00863.x ◽

1999 ◽

Vol 98 (2) ◽

pp. 159-170 ◽

Cited By ~ 59

Author(s):

Gao ◽

Madrenas ◽

Zeng ◽

Cameron ◽

Zhang ◽

...

Keyword(s):

Dendritic Cells ◽

T Cell ◽

Allograft Rejection ◽

Interleukin 10 ◽

Interleukin 12 ◽

Acute Allograft Rejection

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Failure of HIV-exposed CD4+ T cells to activate dendritic cells is reversed by restoration of CD40/CD154 interactions

Blood ◽

10.1182/blood-2005-07-2731 ◽

2006 ◽

Vol 107 (5) ◽

pp. 1989-1995 ◽

Cited By ~ 27

Author(s):

Rui Zhang ◽

Jeffrey D. Lifson ◽

Claire Chougnet

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Hiv Infection ◽

T Cell Activation ◽

Cd4 T Cells ◽

Cell Activation ◽

Interleukin 10 ◽

Interleukin 12 ◽

Cell Mediated Immunity ◽

Hiv Exposed

Because interactions between activated CD4+ T cells and antigen-presenting cells (APCs) are crucial for optimal APC function, defective CD4+ T-cell activation may contribute to APC dysregulation in HIV infection. Here, we show that CD4+ T cells exposed during stimulation to noninfectious HIV having functional envelope glycoproteins failed to provide activation signals to autologous dendritic cells (DCs). Consequently, important DC functions, including production of immunoregulatory cytokines (interleukin-12 p40 and interleukin-10) and up-regulation of costimulatory molecules (CD86, CD40, CD83), as well as the capacity to stimulate naive allogeneic T cells, were all adversely affected. The blunted up-regulation of CD154 in CD4+ T cells that were activated in the presence of noninfectious viruses is likely to be the major underlying mechanism for these defects. Addition of recombinant trimeric CD154 could restore production of cytokines by DCs cocultured with HIV-exposed T cells. Moreover, the functional defects mediated by coculture with HIV-exposed T cells were similar to those following antibody blockade of CD40-CD154 interactions. HIV-mediated blunted CD154 expression may thus play an important role in the suppression of cell-mediated immunity seen in HIV infection.

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Stimulation of Dendritic Cells via CD40 Enhances Immune Responses to Mycobacterium tuberculosisInfection

Infection and Immunity ◽

10.1128/iai.69.4.2456-2461.2001 ◽

2001 ◽

Vol 69 (4) ◽

pp. 2456-2461 ◽

Cited By ~ 43

Author(s):

Caroline Demangel ◽

Umaimainthan Palendira ◽

Carl G. Feng ◽

Andrew W. Heath ◽

Andrew G. D. Bean ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Immune Responses ◽

Protective Efficacy ◽

Interleukin 12 ◽

Ifn Γ ◽

Cellular Immune ◽

Stimulation Of

ABSTRACT The resolution of pulmonary tuberculosis (TB) critically depends on the development of the Th1 type of immune responses, as exemplified by the exacerbation of TB in IL-12-deficient mice. Therefore, vaccination strategies optimizing IL-12 production by antigen-presenting cells (APC) in response to mycobacteria may have enhanced protective efficacy. Since dendritic cells (DC) are the critical APC for activation of CD4+ and CD8+ T cells, we examined whether stimulation of Mycobacterium bovis bacillus Calmette Guérin (BCG)-infected DC via CD40 increased their ability to generate Th1-oriented cellular immune responses. Incubation of DC with an agonistic anti-CD40 antibody activated CD40 signaling in DC, as shown by increased expression of major histocompatibility complex class II and costimulatory molecules, mRNA production for proinflammatory cytokines and interleukin 12 (IL-12) p40. This activation pattern was maintained when DC were stimulated with anti-CD40 antibody and infected with BCG. Importantly, CD40-stimulated BCG-infected DC displayed increased capacity to release bioactive IL-12 and to activate gamma interferon (IFN-γ) producing T cells in vitro. Moreover, when C57BL/6 mice were immunized with these DC and challenged with aerosol Mycobacterium tuberculosis, increased levels of mRNA for IL-12 p40, IL-18, and IFN-γ were present in the draining mediastinal lymph nodes. However, the mycobacterial burden in the lungs was not reduced compared to that in mice immunized with BCG-infected non-CD40-stimulated DC. Therefore, although the manipulation of DC via CD40 is effective for enhancing immune responses to mycobacteria in vivo, additional strategies are required to increase protection against virulent M. tuberculosis infection.

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Targetting Interleukins Involved in Glioblastoma – A New Pharmacological Approach

Journal of Life and Bio Sciences Research ◽

10.38094/jlbsr1330 ◽

2020 ◽

Vol 1 (3) ◽

pp. 82-88

Author(s):

Aetsam Masood ◽

Mahmood Kayani ◽

Sajida Batool

Keyword(s):

Brain Tumor ◽

Brain Tumors ◽

Control Measure ◽

Interleukin 1 ◽

Interleukin 2 ◽

Interleukin 10 ◽

Control Measures ◽

Interleukin 4 ◽

Effective Control ◽

Interleukin 12

Brain tumor is unchecked growth of brain cells disrupting many of its important functions and, affecting molecular regulatory and signaling networks. Glioblastoma is one of the most deleterious tumors of human brain. Cytokines are secondary messenger molecules in many of the immunological and other biochemical reactions. With glioblastoma progression, various cytokines are secreted that either up-regulate or down-regulate many others with immunological function. Interleukins are a family of cytokines acting mainly as immune-regulatory proteins. They have been implicated in brain tumor initiation, progression and invasion. Due to their multiple and varied regulatory roles at every stage of tumor, they are now becoming an attractive target for study in glioblastoma. This mini review briefly summarizes the types and roles of major interleukins and their regulation and, effects in glioblastoma that have been studied so far. Immunotherapeutic aspects are particularly emphasized as the promising therapeutic targets to control brain tumors. Main types of interleukins which are implicated in brain tumors are discussed here which includes interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and interleukin-12 (IL-12). Glioblastoma is one of the most invasive tumor and still lack effective control measures clinically. Conventional treatments like chemotherapy and radiation therapy are not only ineffective in controlling the spread of glioblastoma, but also have damaging and unwanted side effects on healthy cells. Immunotherapy by blocking and/or increasing the action of certain interleukins has proven to be effective control measure in laboratory investigations. Future work extending these findings to clinical and human trials is expected to provide effective treatment measures.

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Autocrine stimulation of interleukin 1 in human adherent synovial lining cells: Down regulation by interferon gamma

Human Immunology ◽

10.1016/0198-8859(91)90098-t ◽

1991 ◽

Vol 31 (4) ◽

pp. 261-270 ◽

Cited By ~ 3

Author(s):

Nathalie Temime ◽

Arlette Joliviere ◽

Danièle Lando ◽

Luc Teyton ◽

Dominique Charron

Keyword(s):

Interferon Gamma ◽

Interleukin 1 ◽

Synovial Lining ◽

Down Regulation ◽

Synovial Lining Cells ◽

Autocrine Stimulation ◽

Stimulation Of

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PSIV-10 Effect of a yeast product supplementation on growth performance, nutrient digestibility and cytokines mRNA expression in weanling piglets reared under low sanitary environment

Journal of Animal Science ◽

10.1093/jas/skz122.317 ◽

2019 ◽

Vol 97 (Supplement_2) ◽

pp. 180-180

Author(s):

Fernando Bravo de Laguna Ortega ◽

Bruno Bertaud ◽

In Ho Kim ◽

Yong Min Kim

Keyword(s):

Gene Expression ◽

Body Weight ◽

Interleukin 1 ◽

Test Procedure ◽

Interleukin 10 ◽

Nutrient Digestibility ◽

Interleukin 12 ◽

Tnf Α ◽

Weanling Piglets ◽

Yeast Product

Abstract The objective of the trial was to evaluate the effect of a novel multi-strains yeast fractions product (MsYF) on performance, digestibility, and gene expression of several cytokines in weanling piglets reared under low sanitary environment (uncleaned). In total, 160 piglets weaned at 24 days (7.21 ± 1.05kg) were distributed in 2 treatments according to body weight and sex: control (CON), and MsYF (CON+2kg/ton of yeast product in the first 14 days post weaning; CON+400g/ton of product between days 14 and 42). Individual body weight (BW) and feed intake (FI) were measured on days 1, 14 and 42. Apparent total tract digestibility (ATTD) of dry matter (DM) and crude protein (CP) was estimated at the end of the experiment using chromium oxide as indigestible marker. On days 7, 14 and 42, 6 piglets per treatment were slaughtered and sampled from the mid-jejunum to measure cytokines mRNA gene expression: tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), toll-like receptor 2 (TLR2), interleukin 1 receptor 1 (IL-1-R1), interleukin 10 (IL-10), interleukin 1β (IL-1β), interleukin 12 (IL-12), interferon gamma (INF- γ), and (GATA3). Data were analyzed by ANOVA using the T-test procedure of SAS (SAS Inst. Inc., Cary, US) with treatment as main effect. Piglets fed MsYF had greater (P < 0.05) final BW and greater (P < 0.01) ADG compared to piglets fed CON. Piglets fed MsYF tended to have greater (P < 0.1) ATTD of DM than piglets fed CON. Supplementation of MsYF down-regulated the expressions of TNF-α, IL-6, and TLR2 on days 7 and 14 (P < 0.01 and P < 0.1 for TNF-α, P < 0.01 and P < 0.001 for IL-6, and P < 0.0001 and P < 0.001 for TLR2) while a reduced (P < 0.01) INF-γ expression occurred in piglets fed MsYF at day 14. In conclusion, supplementation with yeast improved performance, DM digestibility, and may modulate intestinal mucosa inflammation of weanling piglets under low sanitary environment.

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