Corrigendum to “Class B CpG ODN stimulation upregulates expression of TLR21 and IFN-γ in chicken Harderian gland cells” [Vet. Immunol. Immunopathol. 160 (2014) 293–299]

Abstract The synthetic unmethylated oligodeoxynucleotides with CpG motifs (CpG ODN) were shown to activate Toll-like receptor 21 (TLR21) and stimulate the innate and adaptive immune system. In this study we tested the expression of TLR21, interferon (IFN)-γ and interleukin (IL)-1β mRNA in the blood after subcutaneous and intraocular application of the class B CpG ODN in chicken. The relative expression of mRNA of TLR21, IFN-γ and IL-1β were quantified at 3, 6, 12, 24 and 72 h post-stimulation. The study revealed that IFN-γ mRNA expression was significantly upregulated 12 h after subcutaneous stimulation with a high and low dose of ODN CpG, whereas the IL-1β mRNA expression levels were significantly upregulated 3 and 72 h after subcutaneous administration. After intraocular administration, the IL-1β mRNA levels were the highest at 24 h post-application, albeit not specifically. This data indicates that class B CpG ODN has the ability to induce TLR21 response in blood when administered parenterally in chicken. In contrast, intraocular administration of CpG ODN was not able to produce a significant increase in cytokine mRNA expression in blood. The data suggest that additional stimulus, e.g. the antigen, may be needed on the site of mucosal administration to activate systemic immune response.

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Expression of Tyk2 in dendritic cells is required for IL-12, IL-23, and IFN-γ production and the induction of Th1 cell differentiation

Blood ◽

10.1182/blood-2006-11-059246 ◽

2007 ◽

Vol 110 (2) ◽

pp. 553-560 ◽

Cited By ~ 44

Author(s):

Naoki Tokumasa ◽

Akira Suto ◽

Shin-ichiro Kagami ◽

Shunsuke Furuta ◽

Koichi Hirose ◽

...

Keyword(s):

Dendritic Cells ◽

Cell Differentiation ◽

Cpg Odn ◽

T Helper ◽

Dc Functions ◽

Th1 Cell ◽

Th2 Cell ◽

Ifn Γ ◽

Antigen Presenting

Abstract It is well documented that dendritic cells (DCs), representative antigen-presenting cells, are important sources of Th1-promoting cytokines and are actively involved in the regulation of T-helper–cell differentiation. However, the intracellular event that regulates this process is still largely unknown. In this study, we examined the role of Tyk2, a JAK kinase that is involved in the signaling pathway under IL-12 and IL-23, in DC functions. While the differentiation and maturation of DCs was normal in Tyk2-deficient (Tyk2−/−) mice, IL-12–induced Stat4 phosphorylation was diminished in Tyk2−/− DCs. IL-12–induced IFN-γ production was also significantly diminished in Tyk2−/− DCs to levels similar to those in Stat4−/− DCs. Interestingly, Tyk2−/− DCs were defective in IL-12 and IL-23 production upon stimulation with CpG ODN. Furthermore, Tyk2−/− DCs were impaired in their ability to induce Th1-cell differentiation but not Th2-cell differentiation. Taken together, these results indicate that the expression of Tyk2 in DCs is crucial for the production of Th1-promoting cytokines such as IL-12 and IFN-γ from DCs and thereby for the induction of antigen-specific Th1-cell differentiation.

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Protection of BALB/c Mice against Brucella abortus 544 Challenge by Vaccination with Bacterioferritin or P39 Recombinant Proteins with CpG Oligodeoxynucleotides as Adjuvant

Infection and Immunity ◽

10.1128/iai.69.8.4816-4822.2001 ◽

2001 ◽

Vol 69 (8) ◽

pp. 4816-4822 ◽

Cited By ~ 95

Author(s):

Ayman Al-Mariri ◽

Anne Tibor ◽

Pascal Mertens ◽

Xavier De Bolle ◽

Patrick Michel ◽

...

Keyword(s):

Recombinant Proteins ◽

Brucella Abortus ◽

Mononuclear Cells ◽

Brucella Melitensis ◽

Cpg Odn ◽

Peripheral Blood Mononuclear ◽

Recombinant Antigens ◽

Cpg Oligodeoxynucleotides ◽

Ifn Γ

ABSTRACT The P39 and the bacterioferrin (BFR) antigens of Brucella melitensis 16M were previously identified as T dominant antigens able to induce both delayed-type hypersensivity in sensitized guinea pigs and in vitro gamma interferon (IFN-γ) production by peripheral blood mononuclear cells from infected cattle. Here, we analyzed the potential for these antigens to function as a subunitary vaccine against Brucella abortus infection in BALB/c mice, and we characterized the humoral and cellular immune responses induced. Mice were injected with each of the recombinant proteins alone or adjuvanted with either CpG oligodeoxynucleotides (CpG ODN) or non-CpG ODN. Mice immunized with the recombinant antigens with CpG ODN were the only group demonstrating both significant IFN-γ production and T-cell proliferation in response to either Brucella extract or to the respective antigen. The same conclusion holds true for the antibody response, which was only demonstrated in mice immunized with recombinant antigens mixed with CpG ODN. The antibody titers (both immunoglobulin G1 [IgG1] and IgG2a) induced by P39 immunization were higher than the titers induced by BFR (only IgG2a). Using a B. abortus 544 challenge, the level of protection was analyzed and compared to the protection conferred by one immunization with the vaccine strain B19. Immunization with P39 and CpG ODN gave a level of protection comparable to the one conferred by B19 at 4 weeks postchallenge, and the mice were still significantly protected at 8 weeks postchallenge, although to a lesser extent than the B19-vaccinated group. Intriguingly, no protection was detected after BFR vaccination. All other groups did not demonstrate any protection.

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P4-044: THERAPEUTIC POTENTIAL OF INNATE IMMUNITY STIMULATION BY CLASS B CPG ODN IN A TAUOPATHY MOUSE MODEL, RTG4510

Alzheimer s & Dementia ◽

10.1016/j.jalz.2019.06.3703 ◽

2019 ◽

Vol 15 ◽

pp. P1289-P1290

Author(s):

Henrieta Scholtzova ◽

Akash G. Patel ◽

Helen Keizhen Lyo ◽

Elizabeth L. Cho ◽

Yanjie Sun ◽

...

Keyword(s):

Innate Immunity ◽

Mouse Model ◽

Therapeutic Potential ◽

Cpg Odn ◽

Class B

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In ovo administration of CpG ODN induces expression of immune response genes in neonatal chicken spleen

Journal of Veterinary Research ◽

10.1515/jvetres-2017-0050 ◽

2017 ◽

Vol 61 (4) ◽

pp. 451-458 ◽

Cited By ~ 1

Author(s):

Joanna Sajewicz-Krukowska ◽

Monika Olszewska-Tomczyk ◽

Katarzyna Domańska-Blicharz

Keyword(s):

Immune Response ◽

Immune System ◽

High Dose ◽

Cpg Odn ◽

In Ovo ◽

Chicken Spleen ◽

Class B ◽

Synthetic Ligand ◽

The Impact ◽

Experimental Group

AbstractIntroduction:Due to their immunostimulatory properties TLR ligands are used prophylactically to protect against a variety of viral and bacterial pathogens in mammals. Knowledge of the molecular and functional aspects of TLRs is essential for a better understanding of the immune system and resistance to diseases in birds. For that reason, this study attempted to determine the impact of TLR21 stimulation by its synthetic ligand (CpG ODN, class B) on the chicken immune system.Material and Methods:Sixty embryonated chicken eggs were randomly allocated into three groups (control and two experimental groups). On day 18 of embryonic development, chickens in one experimental group were administeredin ovoa low dose of CpG ODN and the birds of the second experimental group were given a high dose of the ligand. Spleens were collected at 1, 2, 5, and 10 days post-hatching (dph) for analysis of IFN-α, IFN-β, IFN-γ, IL-6, and IL-10 expression using qRT-PCR.Results:Significant differences were observed in mRNA expression levels of all the measured cytokines associated with the modulation and regulation of the immune response at different time points.Conclusion:The obtained data clearly demonstrate that immune response induction takes place afterin ovoadministration of class B CpG ODN, and that the ligand has the ability to induce cytokine responses in neonatal chicken spleen.

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CpG Oligodeoxynucleotides Act as Adjuvants that Switch on T Helper 1 (Th1) Immunity

Journal of Experimental Medicine ◽

10.1084/jem.186.10.1623 ◽

1997 ◽

Vol 186 (10) ◽

pp. 1623-1631 ◽

Cited By ~ 735

Author(s):

Rose S. Chu ◽

Oleg S. Targoni ◽

Arthur M. Krieg ◽

Paul V. Lehmann ◽

Clifford V. Harding

Keyword(s):

Immune Response ◽

Immune Responses ◽

Cpg Odn ◽

T Helper ◽

T Helper 1 ◽

Cpg Oligodeoxynucleotides ◽

Cytokine Pattern ◽

Incomplete Freund’S Adjuvant ◽

Ifn Γ ◽

Hen Egg

Synthetic oligodeoxynucleotides (ODN) that contain unmethylated CpG motifs (CpG ODN) induce macrophages to secrete IL-12, which induces interferon (IFN)-γ secretion by natural killer (NK) cells. Since these cytokines can induce T helper 1 (Th1) differentiation, we examined the effects of coadministered CpG ODN on the differentiation of Th responses to hen egg lysozyme (HEL). In both BALB/c (Th2-biased) and B10.D2 (Th1-biased) mice, immunization with HEL in incomplete Freund's adjuvant (IFA) resulted in Th2-dominated immune responses characterized by HEL-specific secretion of IL-5 but not IFN-γ. In contrast, immunization with IFA-HEL plus CpG ODN switched the immune response to a Th1-dominated cytokine pattern, with high levels of HEL-specific IFN-γ secretion and decreased HEL-specific IL-5 production. IFA-HEL plus CpG ODN also induced anti-HEL IgG2a (a Th1-associated isotype), which was not induced by IFA-HEL alone. Control non–CpG ODN did not induce IFN-γ or IgG2a, excepting lesser increases in B10.D2 (Th1-biased) mice. Thus, CpG ODN provide a signal to switch on Th1-dominated responses to coadministered antigen and are potential adjuvants for human vaccines to elicit protective Th1 immunity.

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CpG Oligodeoxynucleotides and Interleukin-12 Improve the Efficacy of Mycobacterium bovis BCG Vaccination in Mice Challenged with M. tuberculosis

Infection and Immunity ◽

10.1128/iai.68.5.2948-2953.2000 ◽

2000 ◽

Vol 68 (5) ◽

pp. 2948-2953 ◽

Cited By ~ 89

Author(s):

Brenda L. Freidag ◽

Genevieve B. Melton ◽

Frank Collins ◽

Dennis M. Klinman ◽

Allen Cheever ◽

...

Keyword(s):

Mycobacterium Bovis ◽

Bacterial Load ◽

Serial Passage ◽

Interleukin 12 ◽

Cpg Odn ◽

Bcg Vaccination ◽

Cpg Oligodeoxynucleotides ◽

Enhanced Production ◽

Ifn Γ

ABSTRACT Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only vaccine approved for prevention of tuberculosis. It has been postulated that serial passage of BCG over the years may have resulted in attenuation of its effectiveness. Because interleukin-12 (IL-12) and oligodeoxynucleotides (ODN) containing cytidine phosphate guanosine (CpG) motifs have been shown to enhance Th1 responses in vivo, they were chosen as adjuvants to increase the effectiveness of BCG vaccination. In this report, mice were vaccinated with BCG with or without IL-12 or CpG ODN and then challenged 6 weeks later via the aerosol route with the Erdman strain of M. tuberculosis. Mice vaccinated with BCG alone showed a 1- to 2-log reduction in bacterial load compared with control mice that did not receive any vaccination prior to M. tuberculosis challenge. Moreover, the bacterial loads of mice vaccinated with BCG plus IL-12 or CpG ODN were a further two- to fivefold lower than those of mice vaccinated with BCG alone. As an immune correlate, the antigen-specific production IFN-γ and mRNA expression in spleen cells prior to challenge were evaluated. Mice vaccinated with BCG plus IL-12 or CpG ODN showed enhanced production of IFN-γ compared with mice vaccinated with BCG alone. Finally, granulomas in BCG-vaccinated mice were smaller and more lymphocyte rich than those in unvaccinated mice; however, the addition of IL-12 or CpG ODN to BCG vaccination did not alter granuloma formation or result in added pulmonary damage. These observations support a role for immune adjuvants given with BCG vaccination to enhance its biologic efficacy.

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Attachment of class B CpG ODN onto DOTAP/DC-chol liposome in nasal vaccine formulations augments antigen-specific immune responses in mice

BMC Research Notes ◽

10.1186/s13104-017-2380-8 ◽

2017 ◽

Vol 10 (1) ◽

Cited By ~ 17

Author(s):

Rui Tada ◽

Shoko Muto ◽

Tomoko Iwata ◽

Akira Hidaka ◽

Hiroshi Kiyono ◽

...

Keyword(s):

Immune Responses ◽

Cpg Odn ◽

Class B ◽

Nasal Vaccine

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CpG Oligodeoxynucleotide 2006 and Miltefosine, a Potential Combination for Treatment of Experimental Visceral Leishmaniasis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00137-11 ◽

2011 ◽

Vol 55 (7) ◽

pp. 3461-3464 ◽

Cited By ~ 18

Author(s):

Suman Gupta ◽

Shraddha A. Sane ◽

Nishi Shakya ◽

Preeti Vishwakarma ◽

W. Haq

Keyword(s):

Visceral Leishmaniasis ◽

Leishmania Donovani ◽

Inhibitory Effect ◽

Rational Approach ◽

Host Use ◽

Cpg Odn ◽

Content Type ◽

Cpg Oligodeoxynucleotide ◽

Class B ◽

Different Doses

ABSTRACTIn view of the severe immunosuppression in visceral leishmaniasis (VL), a rational approach to effectively combat the parasitic scourge would be to enhance the immune status of the host. Use of CpG oligodeoxynucleotide (CpG-ODN) against leishmaniasis has previously been reported, especially as an immunomodulator and adjuvant with various immunogens. In the present study, experiments were carried out with BALB/c mice and hamsters infected withLeishmania donovani. Immunostimulating class B bacterial CpG-ODN namely, ODN-2006, was administered at various doses by the intraperitoneal (i.p.) route. The dose of CpG-ODN-2006 (1 nM/single dose) showing the most antileishmanial activity was given as free and liposomal forms with different doses of miltefosine, namely, 5 and 10 mg/kg of body weight, for 5 days in mice and hamsters, respectively. Among the various groups, mice coadministered liposomal CpG-ODN and miltefosine (5 mg/kg) showed the best inhibitory effect (97% parasite inhibition) compared with free CpG-ODN plus miltefosine and miltefosine, free CpG-ODN, and liposomal CpG-ODN given separately. Similar responses were observed in the case of hamsters, where the combination of liposomal CpG-ODN with miltefosine (10 mg/kg) gave 96% parasite inhibition. Promising antileishmanial efficacy was observed in animals treated with liposomal CpG-ODN and miltefosine.

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