Effective CpG DNA delivery using amphiphilic cycloamylose nanogels

2015 ◽  
Vol 3 (2) ◽  
pp. 256-264 ◽  
Author(s):  
Y. Tahara ◽  
J. Yasuoka ◽  
S. Sawada ◽  
Y. Sasaki ◽  
K. Akiyoshi
Keyword(s):  
Immune Responses ◽  
Cytokine Production ◽  
Dna Delivery ◽  
Cell Uptake ◽  
Cpg Dna ◽  
Cpg Oligodeoxynucleotides

Native CpG oligodeoxynucleotides induce inflammatory immune responses through cytokine production by their effective cell uptake with amphiphilic cationic cycloamylose nanogels.

scholarly journals CpG Oligodeoxynucleotide Developed For Activating Primate Immune Responses Promotes Anti-Tumoral Effect Combine With Neo-Antigen Based mRNA Cancer Vaccine

2021 ◽  
Author(s):  
Rongkuan Hu ◽  
Qin Li ◽  
Jie Ren ◽  
Wei Liu ◽  
Guoqin Jiang
Keyword(s):  
Immune Responses ◽  
Cancer Vaccine ◽  
Cancer Vaccines ◽  
Cytokine Production ◽  
Toll Like Receptor ◽  
Human Pbmc ◽  
Cpg Oligodeoxynucleotides ◽  
Adaptive Immune ◽  
Cpg Oligodeoxynucleotide

Abstract Synthetic phosphorthiolate modified CPG-oligodeoxynucleotides (CPG-ODN) activate innate and adaptive immune responses, which being exploited as a therapeutic approach. Here, we first screened and identified a new CpG-B class ODN (CpG2018B) that effectively stimulates type II interferon both in mouse Plasmacytoid dendritic cells (p-DC) and human PBMC. In addition, CpG2018B promotes cytokine production mainly via toll-like receptor 9 (TLR9) pathways. We further demonstrated that intratumoral (IT) injection of CpG2018B inhibits melanoma growth in syngeneic models and could turn “cold” tumors into “hot” tumors. Then, CpG2018B and mRNA based neo-antigen cancer vaccine were encapsulated into lipid-nanoparticle (LNP) and intratumoral injected into melanoma mice models. Interestingly, vaccination with CpG or mRNA vaccine alone could inhibit tumor growth respectively, while, CpG combine with mRNA vaccine enhanced the anti-tumor effect. At last, we described the long-term safety and tolerability of CpG2018B and mRNA therapy in mice models. In conclusion, we identified a novel CpG-B ODNs to promote immune response and CpG combine with mRNA cancer vaccines are attractive candidate for immune stimulatory sequences (ISS) based therapeutic strategies.

scholarly journals The IL-6-deficient mouse exhibits impaired lymphocytic responses to a vaccine combining liveLeishmania majorand CpG oligodeoxynucleotides

2009 ◽  
Vol 55 (6) ◽  
pp. 705-713 ◽  
Author(s):  
Wenhui Wu ◽  
Luise Weigand ◽  
Susana Mendez
Keyword(s):  
T Cells ◽  
Leishmania Major ◽  
Wild Type ◽  
Cpg Dna ◽  
Cpg Oligodeoxynucleotides ◽  
Inflammatory Stimuli ◽  
Specific Expansion ◽  
Ifn Γ ◽  
Immune Defects ◽  
Draining Lymph Nodes

We have previously reported that vaccination with CpG oligodeoxynucleotides delivered concomitantly with live Leishmania major (Lm/CpG) eliminates lesions associated with live vaccination in C57BL/6 mice. The absence of lesions is at least in part a result of the CpG DNA-mediated activation of dermal dendritic cells to produce cytokines such as interleukin (IL)-6. Wild-type C57BL/6 mice and IL-6−/− mice were immunized with the Lm/CpG vaccine and monitored for the development of lesions. IL-6−/− mice developed extensive, nonhealing lesions following live vaccination. The analysis of the inoculation site and draining lymph nodes of the IL-6−/− mice revealed a constitutive reduction in lymphocyte numbers, particularly CD4+ T cells. Live vaccination resulted in the specific expansion of CD4+Foxp3+ regulatory T cells in the knockout mice, and in a decrease of CD4+ IFN-γ -producing cells. These results indicate that IL-6−/− mice may have collateral immune defects that could influence the development of the natural immune response to pathogens, vaccines, or other inflammatory stimuli.

scholarly journals Enhancement of Mucosal Immunization with Virus-Like Particles of Simian Immunodeficiency Virus

2003 ◽  
Vol 77 (6) ◽  
pp. 3615-3623 ◽  
Author(s):  
Sang-Moo Kang ◽  
Richard W. Compans
Keyword(s):  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 4 ◽  
Cpg Odn ◽  
Virus Like Particles ◽  
Cpg Oligodeoxynucleotides ◽  
Immunodeficiency Virus ◽  
Helper Cell Type ◽  
Spleen And Lymph Nodes

ABSTRACT Cholera toxin (CT) is the most potent known mucosal adjuvant, but its toxicity precludes its use in humans. Here, in an attempt to develop safe and effective mucosal adjuvants, we compared immune responses to simian immunodeficiency virus (SIV) virus-like particles (VLPs) after intranasal coimmunization with RANTES, CpG oligodeoxynucleotides (ODN), or CT. Antibody analysis demonstrated that RANTES and CpG ODN had capacities for mucosal adjuvanticity, i.e., for enhancing serum and vaginal antibodies specific to SIV Env, similar to those for CT. RANTES and CpG ODN skewed serum antibodies predominantly to the immunoglobulin G2a isotype. Most importantly, RANTES and CpG ODN were more effective than CT in increasing neutralizing titers of both serum and vaginal antibodies. After intranasal coadministration with VLPs, RANTES or CpG ODN also induced increased levels of gamma interferon (IFN-γ)-producing lymphocyte and cytotoxic T-lymphocyte activities in both spleen and lymph nodes but did not increase the levels of interleukin-4-producing lymphocytes. The results suggest that RANTES and CpG ODN enhance immune responses in a T-helper-cell-type-1 (Th1)-oriented manner and that they can be used as effective mucosal adjuvants for enhancing both humoral and cellular immune responses in the context of VLPs, which are particulate antigens.

Lidocaine depresses splenocyte immune functions following trauma-hemorrhage in mice

2006 ◽  
Vol 291 (5) ◽  
pp. C1049-C1055 ◽  
Author(s):  
Takashi Kawasaki ◽  
Mashkoor A. Choudhry ◽  
Martin G. Schwacha ◽  
Kirby I. Bland ◽  
Irshad H. Chaudry
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
Immune Responses ◽  
Cytokine Production ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Sham Operation ◽  
Mapk Activation ◽  
Midline Laparotomy ◽  
Marrow Cells

Traumatic and/or surgical injury as well as hemorrhage induces profound suppression of cellular immunity. Although local anesthetics have been shown to impair immune responses, it remains unclear whether lidocaine affects lymphocyte functions following trauma-hemorrhage (T-H). We hypothesized that lidocaine will potentiate the suppression of lymphocyte functions after T-H. To test this, we randomly assigned male C3H/HeN (6–8 wk) mice to sham operation or T-H. T-H was induced by midline laparotomy and ∼90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (4× shed blood volume in the form of Ringer lactate). Two hours later, the mice were killed and splenocytes and bone marrow cells were isolated. The effects of lidocaine on concanavalin A-stimulated splenocyte proliferation and cytokine production in both sham-operated and T-H mice were assessed. The effects of lidocaine on LPS-stimulated bone marrow cell proliferation and cytokine production were also assessed. The results indicate that T-H suppresses cell proliferation, Th1 cytokine production, and MAPK activation in splenocytes. In contrast, cell proliferation, cytokine production, and MAPK activation in bone marrow cells were significantly higher 2 h after T-H compared with shams. Lidocaine depressed immune responses in splenocytes; however, it had no effect in bone marrow cells in either sham or T-H mice. The enhanced immunosuppressive effects of lidocaine could contribute to the host's enhanced susceptibility to infection following T-H.

scholarly journals Mutual Interplay of Host Immune System and Gut Microbiota in the Immunopathology of Atherosclerosis

2020 ◽  
Vol 21 (22) ◽  
pp. 8729 ◽  
Author(s):  
Chih-Fan Yeh ◽  
Ying-Hsien Chen ◽  
Sheng-Fu Liu ◽  
Hsien-Li Kao ◽  
Ming-Shiang Wu ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Cytokine Production ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Inflammasome Activation ◽  
Host Immune System ◽  
Gut Permeability ◽  
And Function ◽  
Progression Of Atherosclerosis

Inflammation is the key for the initiation and progression of atherosclerosis. Accumulating evidence has revealed that an altered gut microbiome (dysbiosis) triggers both local and systemic inflammation to cause chronic inflammatory diseases, including atherosclerosis. There have been some microbiome-relevant pro-inflammatory mechanisms proposed to link the relationships between dysbiosis and atherosclerosis such as gut permeability disruption, trigger of innate immunity from lipopolysaccharide (LPS), and generation of proatherogenic metabolites, such as trimethylamine N-oxide (TMAO). Meanwhile, immune responses, such as inflammasome activation and cytokine production, could reshape both composition and function of the microbiota. In fact, the immune system delicately modulates the interplay between microbiota and atherogenesis. Recent clinical trials have suggested the potential of immunomodulation as a treatment strategy of atherosclerosis. Here in this review, we present current knowledge regarding to the roles of microbiota in contributing atherosclerotic pathogenesis and highlight translational perspectives by discussing the mutual interplay between microbiota and immune system on atherogenesis.

scholarly journals Mycobacterium tuberculosisinhibits human innate immune responses via the production of TLR2 antagonist glycolipids

2017 ◽  
Vol 114 (42) ◽  
pp. 11205-11210 ◽  
Author(s):  
Landry Blanc ◽  
Martine Gilleron ◽  
Jacques Prandi ◽  
Ok-ryul Song ◽  
Mi-Seon Jang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Molecular Mechanisms ◽  
Cytokine Production ◽  
Cell Envelope ◽  
Costimulatory Molecule ◽  
Immune Defense ◽  
Innate Immune ◽  
Host Cells ◽  
Innate Immune Responses ◽  
Reporter System

Mycobacterium tuberculosisis a major human pathogen that is able to survive inside host cells and resist immune clearance. Most particularly, it inhibits several arms of the innate immune response, including phagosome maturation or cytokine production. To better understand the molecular mechanisms by whichM. tuberculosiscircumvents host immune defenses, we used a transposon mutant library generated in a virulent clinical isolate ofM. tuberculosisof the W/Beijing family to infect human macrophages, utilizing a cell line derivative of THP-1 cells expressing a reporter system for activation of the transcription factor NF-κB, a key regulator of innate immunity. We identified severalM. tuberculosismutants inducing a NF-κB activation stronger than that of the wild-type strain. One of these mutants was found to be deficient for the synthesis of cell envelope glycolipids, namely sulfoglycolipids, suggesting that the latter can interfere with innate immune responses. Using natural and synthetic molecular variants, we determined that sulfoglycolipids inhibit NF-κB activation and subsequent cytokine production or costimulatory molecule expression by acting as competitive antagonists of Toll-like receptor 2, thereby inhibiting the recognition ofM. tuberculosisby this receptor. Our study reveals that producing glycolipid antagonists of pattern recognition receptors is a strategy used byM. tuberculosisto undermine innate immune defense. Sulfoglycolipids are major and specific lipids ofM. tuberculosis, considered for decades as virulence factors of the bacilli. Our study uncovers a mechanism by which they may contribute toM. tuberculosisvirulence.

Fibronectin inhibits cytokine production induced by CpG DNA in macrophages without direct binding to DNA

Cytokine ◽  
2012 ◽  
Vol 60 (1) ◽  
pp. 162-170 ◽  
Author(s):  
Hiroyuki Yoshida ◽  
Makiya Nishikawa ◽  
Sachiyo Yasuda ◽  
Hiroyasu Toyota ◽  
Tsuyoshi Kiyota ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Cpg Dna ◽  
Direct Binding

scholarly journals CpG Oligodeoxynucleotides Increase the Susceptibility of Normal Mice to Infection by Candida albicans

2005 ◽  
Vol 73 (9) ◽  
pp. 6154-6156 ◽  
Author(s):  
Shuichi Ito ◽  
Joao Pedras-Vasconcelos ◽  
Dennis M. Klinman
Keyword(s):  
Immune Response ◽  
Candida Albicans ◽  
Innate Immune Response ◽  
Host Resistance ◽  
Cytokine Production ◽  
Innate Immune ◽  
Interleukin 12 ◽  
Cpg Oligodeoxynucleotides ◽  
Cpg Motifs ◽  
Resistance To Infection

ABSTRACT Synthetic oligodeoxynucleotides containing CpG motifs trigger an innate immune response that typically increases host resistance to infection. Yet CpG treatment reduces the resistance of normal mice to Candida albicans infection. This effect is mediated by CpG-induced interleukin-12, indicating that CpG-dependent cytokine production may have adverse consequences for the host.

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