scholarly journals Expression of Toll-Like Receptor 2 by Dendritic Cells Is Essential for the DnaJ-ΔA146Ply-Mediated Th1 Immune Response against Streptococcus pneumoniae

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Xiaofang Wang ◽  
Taixian Yuan ◽  
Jun Yuan ◽  
Yufeng Su ◽  
Xiaoyu Sun ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cell ◽  
Protective Immunity ◽  
Survival Rates ◽  
Pneumococcal Infection ◽  
Toll Like Receptor ◽  
Pneumococcal Strain ◽  
Ifn Γ ◽  
Subcutaneous Immunization ◽  
Th1 Immune Response

ABSTRACT The fusion protein DnaJ-ΔA146Ply could induce cross-protective immunity against pneumococcal infection via mucosal and subcutaneous immunization in mice in the absence of additional adjuvants. DnaJ and Ply are both Toll-like receptor 4 (TLR4) but not TLR2 ligands. However, we found that TLR2 −/− mice immunized subcutaneously with DnaJ-ΔA146Ply showed significantly lower survival rates and higher bacterial loads in nasal washes than did wild-type (WT) mice after being challenged with pneumococcal strain D39 or 19F. The gamma interferon (IFN-γ) level in splenocytes decreased in TLR2 −/− mice, indicating that Th1 immunity elicited by DnaJ-ΔA146Ply was impaired in these mice. We explored the mechanism of protective immunity conferred by DnaJ-ΔA146Ply and the role of TLR2 in this process. DnaJ-ΔA146Ply effectively promoted dendritic cell (DC) maturation via TLR4 but not the TLR2 signaling pathway. In a DnaJ-ΔA146Ply-treated DC and naive CD4 + T cell coculture system, the deficiency of TLR2 in DCs resulted in a significant decline of IFN-γ production and Th1 subset differentiation. The same effect was observed in adoptive-transfer experiments. In addition, TLR2 −/− DCs showed remarkably lower levels of the Th1-polarizing cytokine IL-12p70 than did WT DCs, suggesting that TLR2 was indispensable for DnaJ-ΔA146Ply-induced IL-12 production and Th1 proliferation. Thus, our findings illustrate that dendritic cell expression of TLR2 is essential for optimal Th1 immune response against pneumococci in mice immunized subcutaneously with DnaJ-ΔA146Ply.

scholarly journals T-Cell Immune Response Assessment as a Complement to Serology and Intranasal Protection Assays in Determining the Protective Immunity Induced by Acellular Pertussis Vaccines in Mice

2003 ◽  
Vol 10 (4) ◽  
pp. 637-642 ◽  
Author(s):  
C. M. Ausiello ◽  
R. Lande ◽  
P. Stefanelli ◽  
C. Fazio ◽  
G. Fedele ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Pertussis Toxin ◽  
Protective Immunity ◽  
T Cell Responses ◽  
Additional Tool ◽  
Cell Responses ◽  
T Cell Immune Responses ◽  
Ifn Γ

ABSTRACT The relative value of antibodies and/or T-cell immune responses to Bordetella pertussis antigens in the immunity induced by acellular pertussis (aP) vaccines is still an open issue, probably due to the incomplete knowledge on the mechanisms of protective immunity to pertussis. The relevance of T-cell immune responses in protection from pertussis has been demonstrated in murine and human models of infection; thus, in this study, the ability of different vaccine preparations of three component (pertussis toxin, filamentous hemagglutinin, and pertactin) aP vaccines to induce T-cell responses was investigated in mice. All vaccine preparations examined passed the immunogenicity control test, based on antibody titer assessment, according to European Pharmacopoeia standards, and protected mice from B. pertussis intranasal challenge, but not all preparations were able to prime T cells to pertussis toxin, the specific B. pertussis antigen. In particular, one vaccine preparation was unable to induce proliferation and gamma interferon (IFN-γ) production while the other two gave borderline results. The evaluation of T-cell responses to pertussis toxin antigen may provide information on the protective immunity induced by aP vaccines in animal models. Considering the critical role of the axis interleukin-12-IFN-γ for protection from pertussis, our results suggest that testing the induction of a key protective cytokine such as IFN-γ could be an additional tool for the evaluation of the immune response induced by aP vaccines.

scholarly journals Influence of Immunotherapy with Autologous Dendritic Cells on Innate and Adaptive Immune Response in Cancer

2013 ◽  
Vol 7 ◽  
pp. CMO.S12268 ◽  
Author(s):  
Bruna F. Matias ◽  
Tânia M. De Oliveira ◽  
Cláudia M. Rodrigues ◽  
Douglas R. Abdalla ◽  
Letícia Montes ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
Dendritic Cell ◽  
B Lymphocytes ◽  
Dendritic Cell Vaccine ◽  
Cell Vaccine ◽  
Enzyme Linked Immunosorbent Assay ◽  
Autologous Dendritic Cell ◽  
Tnf Α ◽  
Ifn Γ

The objective of this study was to evaluate some of the mechanisms involved in the activation of the immune system in patients with advanced-stage cancer (n = 7) who received an autologous dendritic cell vaccine. We examined the immune response mediated by macrophages (CD14+), natural killer cells (CD56+), and B lymphocytes (CD19+) by flow cytometry and assessed the expression of Th1 (IFN-γ, TNF-α, IL-2, and IL-12), Th2 (IL-4), and Treg (TGF-β) cytokines by flow cytometry and an enzyme-linked immunosorbent assay. The CD14+ TNF-α+ population was significantly increased ( P < 0.04) when patients received the vaccine; IL-2 expression in both NK cells and in B lymphocytes was increased after a transient initial increase showed a nearly significant decrease ( P < 0.07 and P < 0.06 respectively), whereas the CD19+ and CD56+ populations did not show significant changes. Dendritic cell-based immunotherapy led to increased secretion of IFN-γ and IL-12 and reduced secretion of TGF-β. In conclusion, it is likely that the autologous dendritic cell vaccine stimulated the immune cells from the peripheral blood of patients with cancer and generally increased the production of Th1 cytokines, which are related to immunomodulatory responses against cancer.

scholarly journals Vaccination with Lentiviral Vector Expressing thenfa1Gene Confers a Protective Immune Response to Mice Infected with Naegleria fowleri

2013 ◽  
Vol 20 (7) ◽  
pp. 1055-1060 ◽  
Author(s):  
Jong-Hyun Kim ◽  
Hae-Jin Sohn ◽  
Jinyoung Lee ◽  
Hee-Jong Yang ◽  
Yong-Joon Chwae ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Viral Vector ◽  
Lentiviral Vector ◽  
Survival Rates ◽  
Dna Vaccination ◽  
Naegleria Fowleri ◽  
Content Type ◽  
Ifn Γ ◽  
Nægleria Fowleri

ABSTRACTNaegleria fowleri, a pathogenic free-living amoeba, causes fatal primary amoebic meningoencephalitis (PAM) in humans and animals. Thenfa1gene (360 bp), cloned from a cDNA library ofN. fowleri, produces a 13.1-kDa recombinant protein which is located on pseudopodia, particularly the food cup structure. Thenfa1gene plays an important role in the pathogenesis ofN. fowleriinfection. To examine the effect ofnfa1DNA vaccination againstN. fowleriinfection, we constructed a lentiviral vector (pCDH) expressing thenfa1gene. For thein vivomouse study, BALB/c mice were intranasally vaccinated with viral particles of a viral vector expressing thenfa1gene. To evaluate the effect of vaccination and immune responses of mice, we analyzed the IgG levels (IgG, IgG1, and IgG2a), cytokine induction (interleukin-4 [IL-4] and gamma interferon [IFN-γ]), and survival rates of mice that developed PAM. The levels of both IgG and IgG subclasses (IgG1 and IgG2a) in vaccinated mice were significantly increased. The cytokine analysis showed that vaccinated mice exhibited greater IL-4 and IFN-γ production than the other control groups, suggesting a Th1/Th2 mixed-type immune response. In vaccinated mice, high levels of Nfa1-specific IgG antibodies continued until 12 weeks postvaccination. The mice vaccinated with viral vector expressing thenfa1gene also exhibited significantly higher survival rates (90%) after challenge withN. fowleritrophozoites. Finally, thenfa1vaccination effectively induced protective immunity by humoral and cellular immune responses inN. fowleri-infected mice. These results suggest that DNA vaccination using a viral vector may be a potential tool againstN. fowleriinfection.

scholarly journals Reciprocal Protective Immunity againstBordetella pertussis and Bordetella parapertussis in a Murine Model of Respiratory Infection

2001 ◽  
Vol 69 (11) ◽  
pp. 6981-6986 ◽  
Author(s):  
Mineo Watanabe ◽  
Masaaki Nagai
Keyword(s):  
Immune Response ◽  
Respiratory Infection ◽  
Murine Model ◽  
Protective Immunity ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Spleen Cells ◽  
Bordetella Parapertussis ◽  
Ifn Γ

ABSTRACT The protective immunity induced by infection with Bordetella pertussis and with Bordetella parapertussis was examined in a murine model of respiratory infection. Convalescent mice that had been infected by aerosol with B. pertussis or with B. parapertussis exhibited a protective immune response against B. pertussis and also against B. parapertussis. Anti-filamentous hemagglutinin (anti-FHA) serum immunoglobulin G (IgG) and anti-FHA lung IgA antibodies were detected in both mice infected with B. pertussis and those infected with B. parapertussis. Antibodies against pertussis toxin (anti-PT) and against killed B. pertussis cells were detected in mice infected with B. pertussis. Pertactin-specific antibodies and antibodies against killed B. parapertussis cells were detected in mice infected with B. parapertussis. Spleen cells from mice infected with B. pertussis secreted interferon-γ (IFN-γ) in response to stimulation by FHA or PT. Spleen cells from mice infected with B. parapertussis also secreted IFN-γ in response to FHA. Interleukin-4 was not produced in response to any of the antigens tested. The profiles of cytokine secretion in vitro revealed induction of a Th1-biased immune response during convalescence from infection by B. pertussis and byB. parapertussis. It is possible that Th1 and Th2 responses against FHA might be related to the reciprocal protection achieved in our murine model.

scholarly journals Mycobacterium abscessus MAB2560 induces maturation of dendritic cells via Toll-like receptor 4 and drives Th1 immune response

BMB Reports ◽  
2014 ◽  
Vol 47 (9) ◽  
pp. 512-517 ◽  
Author(s):  
Su Jung Lee ◽  
Sung Jae Shin ◽  
Seung Jun Lee ◽  
Moon Hee Lee ◽  
Tae Heung Kang ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Mycobacterium Abscessus ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Th1 Immune Response

Selection of Criteria for Assessing Protective Immunity at Different Times of Experimental Tularemia in a Mouse Model

2021 ◽  
Vol 37 (4) ◽  
pp. 65-77
Author(s):  
G.M. Titareva ◽  
A.N. Mokrievich ◽  
T.I. Kombarova ◽  
G.M. Vakhrameeva ◽  
R.I. Mironova ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Vaccine Strain ◽  
Protective Immunity ◽  
T And B Cells ◽  
Immunological Parameters ◽  
Protective Properties ◽  
Virulent Strains ◽  
Ifn Γ

It is known that the body's defense against infection by the intracellular bacterium Francisella tularensis is provided by the activation of the cellular and humoral immune response. However, their role in long-term protection (25 years and more) against virulent strains of F. tularensis is not well understood. The identification of clear criteria for assessing protective immunity to the tularemia causative agent at different times after vaccination will make it possible to more efficiently develop new genetically determined vaccine strains. The goal of our research was to select and assess immunological parameters reflecting the protective properties of the vaccine strain F. tularensis 15 NIIEG and its derivatives, F. tularensis 15/23-1∆recA and F. tularensis 15/ 23-1/sodB∆recA, in the long term after immunization. To assess the functional activity of T and B cells, flow cytometry was used.The assessment of the production of cytokines IFN-γ, IL-4, IL-10, IL-17A and titers of specific class G immunoglobulins to F. tularensis lipopolysaccharide (LPS)in blood serum was performed by ELISA on days 30, 60, 90 and 180 after immunization. Evaluation of the protective properties of vaccine preparations in the above-mentioned terms was carried out after subcutaneous infection with test-infecting virulent strains, Schu and 503 of tularensis and holarctica subspecies, respectively. It was shown that vaccination with the studied strains in 100% of cases protected from infection with the strain 503 of the holarctica subspecies, analogous to the vaccine strain. When infected with a virulent Schu strain of the hetrologous tularensis subspecies, a decrease in the effectiveness of protection was observed starting from 60 days after immunization. Evaluation of immunological parameters showed that at all studied periods after immunization, IgG antibodies to F. tularensis LPS were detected in the blood sera of immunized mice. In vitro experiments on stimulation of immune response in spleen lymphocytes of vaccinated mice to the F. tularensis antigen showed a significant increase in the level of secreted IFN-γ, a slight increase in secreted IL-10 and an enhanced expression of the CD69 molecule on the surface of T and B cells. Thus, the level of IFN-γ and the expression of the CD69 molecule on the surface of T and B cells in response to restimulation of lymphocytes of immune animals with tularemia antigen can serve as criteria for immune protection in experimental tularemia in a mouse model at different times after vaccination. Key words: vaccine strain, Fransicella tularensis, immunogenicity, protection, memory T cells, IgG, cellular immunity Funding - The work was supported by the Branch Program of the Russian Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing.

scholarly journals Characterization and Modulation of the Immunosuppressive Phase of Sepsis

2010 ◽  
Vol 78 (4) ◽  
pp. 1582-1592 ◽  
Author(s):  
Jared T. Muenzer ◽  
Christopher G. Davis ◽  
Kathy Chang ◽  
Robert E. Schmidt ◽  
W. Michael Dunne ◽  
...  
Keyword(s):  
Immune Response ◽  
Proinflammatory Cytokines ◽  
Secondary Infection ◽  
Survival Rates ◽  
Cecal Ligation ◽  
Decisive Role ◽  
Lavage Fluid ◽  
Interleukin 10 ◽  
Secondary Injury ◽  
Ifn Γ

ABSTRACT Sepsis continues to cause significant morbidity and mortality in critically ill patients. Studies of patients and animal models have revealed that changes in the immune response during sepsis play a decisive role in the outcome. Using a clinically relevant two-hit model of sepsis, i.e., cecal ligation and puncture (CLP) followed by the induction of Pseudomonas aeruginosa pneumonia, we characterized the host immune response. Second, AS101 [ammonium trichloro(dioxoethylene-o,o′)tellurate], a compound that blocks interleukin 10 (IL-10), a key mediator of immunosuppression in sepsis, was tested for its ability to reverse immunoparalysis and improve survival. Mice subjected to pneumonia following CLP had different survival rates depending upon the timing of the secondary injury. Animals challenged with P. aeruginosa at 4 days post-CLP had ∼40% survival, whereas animals challenged at 7 days had 85% survival. This improvement in survival was associated with decreased lymphocyte apoptosis, restoration of innate cell populations, increased proinflammatory cytokines, and restoration of gamma interferon (IFN-γ) production by stimulated splenocytes. These animals also showed significantly less P. aeruginosa growth from blood and bronchoalveolar lavage fluid. Importantly, AS101 improved survival after secondary injury 4 days following CLP. This increased survival was associated with many of the same findings observed in the 7-day group, i.e., restoration of IFN-γ production, increased proinflammatory cytokines, and decreased bacterial growth. Collectively, these studies demonstrate that immunosuppression following initial septic insult increases susceptibility to secondary infection. However, by 7 days post-CLP, the host's immune system has recovered sufficiently to mount an effective immune response. Modulation of the immunosuppressive phase of sepsis may aid in the development of new therapeutic strategies.

Sign in / Sign up

Export Citation Format

Share Document