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

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 1465 ◽  
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.

scholarly journals The Frequency of BDCA3-Positive Dendritic Cells Is Increased in the Peripheral Circulation of Kenyan Children with Severe Malaria

2006 ◽  
Vol 74 (12) ◽  
pp. 6700-6706 ◽  
Author(s):  
Britta C. Urban ◽  
Damien Cordery ◽  
Mohammed J. Shafi ◽  
Peter C. Bull ◽  
Christopher I. Newbold ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Severe Malaria ◽  
Peripheral Blood ◽  
Plasma Concentrations ◽  
Peripheral Circulation ◽  
Interleukin 10 ◽  
Low Concentrations ◽  
High Concentrations ◽  
And Function ◽  
Antigen Presenting

ABSTRACT The ability of Plasmodium falciparum-infected erythrocytes to adhere to host endothelial cells via receptor molecules such as ICAM-1 and CD36 is considered a hallmark for the development of severe malaria syndromes. These molecules are also expressed on leukocytes such as dendritic cells. Dendritic cells are antigen-presenting cells that are crucial for the initiation of adaptive immune responses. In many human diseases, their frequency and function is perturbed. We analyzed the frequency of peripheral blood dendritic cell subsets and the plasma concentrations of interleukin-10 (IL-10) and IL-12 in Kenyan children with severe malaria and during convalescence and related these parameters to the adhesion phenotype of the acute parasite isolates. The frequency of CD1c+ dendritic cells in children with acute malaria was comparable to that in healthy controls, but the frequency of BDCA3+ dendritic cells was significantly increased. Analysis of the adhesion phenotypes of parasite isolates revealed that adhesion to ICAM-1 was associated with the frequency of peripheral blood CD1c+ dendritic cells, whereas the adhesion of infected erythrocytes to CD36 correlated with high concentrations of IL-10 and low concentrations of IL-12 in plasma.

Curcumin: a dietary phytochemical for targeting the phenotype and function of dendritic cells

2020 ◽  
Vol 27 ◽  
Author(s):  
Kaveh Rahimi ◽  
Kambiz Hassanzadeh ◽  
Hashem Khanbabaei ◽  
Saeed Mohammadian Haftcheshmeh ◽  
Abbas Ahmadi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Intracellular Signaling ◽  
T Helper 1 ◽  
Cytokines And Chemokines ◽  
Wide Range ◽  
Health And Disease ◽  
And Function ◽  
Antigen Presenting ◽  
Tolerogenic Dcs

: Dendritic cells (DCs) are the most powerful antigen-presenting cells which link the innate and adaptive immune responses. Depending on the context DCs initiate the immune responses or contribute to immune tolerance. Any disturbance in their phenotypes and functions may initiate inflammatory or autoimmune diseases. Hence, dysregulated DCs are the most attractive pharmacological target for the development of new therapies aiming at reducing their immunogenicity and at enhancing their tolerogenicity. Curcumin is the polyphenolic phytochemical component of the spice turmeric with a wide range of pharmacological activities. It acts in several ways as a modulator of DCs and converts them into tolerogenic DCs. Tolerogenic DCs possess anti-inflammatory and immunomodulatory activities that regulate the immune responses in health and disease. Curcumin by blocking maturation markers, cytokines and chemokines expression, and disrupting the antigen-presenting machinery of DCs render them non- or hypo-responsive to immunostimulants. It also reduces the expression of co-stimulatory and adhesion molecules on DCs and prevents them from both migration and antigen presentation but enhances their endocytosis capacity. Hence, curcumin causes DCs-inducing regulatory T cells and dampens CD4+ T helper 1 (Th1), Th2, and Th17 polarization. Inhibition of transcription factors such as NF-κB, AP-1, MAPKs (p38, JNK, ERK) and other intracellular signaling molecules such as JAK/STAT/SOCS provide a plausible explanation for most of these observations. In this review, we summarize the potential effects of curcumin on the phenotypes and functions of DCs as the key players in orchestration, stimulation, and modulation of the immune responses.

Functional domains of HSP70 stimulate generation of cytokines and chemokines, maturation of dendritic cells and adjuvanticity

2004 ◽  
Vol 32 (4) ◽  
pp. 629-632 ◽  
Author(s):  
T. Lehner ◽  
Y. Wang ◽  
T. Whittall ◽  
E. McGowan ◽  
C.G. Kelly ◽  
...  
Keyword(s):  
Amino Acids ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Cd40 Ligand ◽  
Interleukin 12 ◽  
Cytokines And Chemokines ◽  
Cc Chemokines ◽  
Factor Α ◽  
Antigen Presenting ◽  
Necrosis Factor

Microbial HSP70 (heat-shock protein 70) consists of three functionally distinct domains: an N-terminal 44 kDa ATPase portion (amino acids 1–358), followed by an 18 kDa peptide-binding domain (amino acids 359–494) and a C-terminal 10 kDa fragment (amino acids 495–609). Immunological functions of these three different domains in stimulating monocytes and dendritic cells have not been fully defined. However, the C-terminal portion (amino acids 359–610) stimulates the production of CC chemokines, IL-12 (interleukin-12), TNFα(tumour necrosis factor α), NO and maturation of dendritic cells and also functions as an adjuvant in the induction of immune responses. In contrast, the ATPase domain of microbial HSP70 mostly lacks these functions. Since the receptor for HSP70 is CD40, which with its CD40 ligand constitutes a major co-stimulatory pathway in the interaction between antigen-presenting cells and T-cells, HSP70 may function as an alternative ligand to CD40L. HSP70–CD40 interaction has been demonstrated in non-human primates to play a role in HIV infection, in protection against Mycobacterium tuberculosis and in conversion of tolerance to immunity.

scholarly journals Susceptibility to Polyomavirus-Induced Tumors in Inbred Mice: Role of Innate Immune Responses

2002 ◽  
Vol 76 (19) ◽  
pp. 9657-9663 ◽  
Author(s):  
Palanivel Velupillai ◽  
John P. Carroll ◽  
Thomas L. Benjamin
Keyword(s):  
Antigen Presenting Cells ◽  
Interleukin 10 ◽  
Cytokine Response ◽  
Innate Immune ◽  
Interleukin 12 ◽  
Cytokine Responses ◽  
Induced Tumors ◽  
Antigen Presenting ◽  
Type 1 Cytokine

ABSTRACT Mice of the PERA/Ei strain (PE mice) are highly susceptible to tumor induction by polyomavirus and transmit their susceptibility in a dominant manner in crosses with resistant C57BR/cdJ mice (BR mice). BR mice respond to polyomavirus infection with a type 1 cytokine response and develop effective cell-mediated immunity to the virus-induced tumors. By enumerating virus-specific CD8+ T cells and measuring cytokine responses, we show that the susceptibility of PE mice is due to the absence of a type 1 cytokine response and a concomitant failure to sustain virus-specific cytotoxic T lymphocytes. (PE × BR)F1 mice showed an initial type 1 response that became skewed toward type 2. Culture supernatants of splenocytes from infected PE mice stimulated in vitro contained high levels of interleukin-10 and no detectable gamma interferon, while those from BR mice showed the opposite pattern. Differences in the innate immune response to polyomavirus by antigen-presenting cells in PE mice and BR mice led to polarization of T-cell cytokine responses. Adherent cells from spleens of infected BR mice produced high levels of interleukin-12, while those from infected PE and F1 mice produced predominantly interleukin-10. PE and F1 mice infected by polyomavirus responded with increases in antigen-presenting cells expressing B7.2 costimulatory molecules, whereas BR mice responded with increased expression of B7.1. Administration of recombinant interleukin-12 along with virus resulted in partial protection of PE mice and provided complete protection against tumor development in F1 animals.

scholarly journals Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells

2008 ◽  
Vol 205 (6) ◽  
pp. 1447-1461 ◽  
Author(s):  
Franca Gerosa ◽  
Barbara Baldani-Guerra ◽  
Lyudmila A. Lyakh ◽  
Giovanna Batoni ◽  
Semih Esin ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 12 ◽  
Mycobacterium Tuberculosis H37rv ◽  
Interleukin 23 ◽  
Human Dendritic Cells ◽  
Differential Ability ◽  
Antigen Presenting ◽  
Tlr2 Ligands

We analyzed interleukin (IL) 12 and IL-23 production by monocyte-derived dendritic cells (mono-DCs). Mycobacterium tuberculosis H37Rv and zymosan preferentially induced IL-23. IL-23 but not IL-12 was efficiently induced by the combination of nucleotide-binding oligodimerization domain and Toll-like receptor (TLR) 2 ligands, which mimics activation by M. tuberculosis, or by the human dectin-1 ligand β-glucan alone or in combination with TLR2 ligands, mimicking induction by zymosan. TLR2 ligands inhibited IL-12 and increased IL-23 production. DC priming with interferon (IFN) γ strongly increased IL-12 production, but was not required for IL-23 production and inhibited IL-23 production induced by β-glucan. The pattern of IL-12 and IL-23 induction was reflected in accumulation of the IL-12p35 and IL-23p19 transcripts, respectively, but not IL-12/23p40. Although IL-23, transforming growth factor β, and IL-6 contained in the supernatants of activated mono-DCs played a role in the induction of IL-17 by human CD4+ T cells, IL-1β, in combination with one or more of those factors, was required for IL-17 production, and its production determined the differential ability of the stimuli used to elicit mono-DCs to produce soluble factors directing IL-17 production. Thus, the differential ability of pathogens to induce antigen-presenting cells to produce cytokines regulates the immune response to infection.

Expression and function of Toll-like receptors on dendritic cells and other antigen presenting cells from non-human primates

2008 ◽  
Vol 125 (1-2) ◽  
pp. 18-30 ◽  
Author(s):  
Chutitorn Ketloy ◽  
Anneke Engering ◽  
Utaiwan Srichairatanakul ◽  
Amporn Limsalakpetch ◽  
Kosol Yongvanitchit ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Antigen Presenting Cells ◽  
Toll Like Receptors ◽  
And Function ◽  
Antigen Presenting

scholarly journals Infection of Human Dendritic Cells with a Mycobacterium tuberculosis sigE Mutant Stimulates Production of High Levels of Interleukin-10 but Low Levels of CXCL10: Impact on the T-Cell Response

2006 ◽  
Vol 74 (6) ◽  
pp. 3296-3304 ◽  
Author(s):  
Elena Giacomini ◽  
Ambar Sotolongo ◽  
Elisabetta Iona ◽  
Martina Severa ◽  
Maria Elena Remoli ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Mycobacterium Tuberculosis ◽  
Human Monocyte ◽  
Interleukin 10 ◽  
T Cell Response ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Effector Cells ◽  
Human Dendritic Cells

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.

Sign in / Sign up

Export Citation Format

Share Document