scholarly journals Chronic Active Hepatitis Induced by Helicobacter hepaticus in the A/JCr Mouse Is Associated with a Th1 Cell-Mediated Immune Response

1998 ◽  
Vol 66 (7) ◽  
pp. 3142-3148 ◽  
Author(s):  
M. T. Whary ◽  
T. J. Morgan ◽  
C. A. Dangler ◽  
K. J. Gaudes ◽  
N. S. Taylor ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Chronic Active Hepatitis ◽  
Outer Membrane Proteins ◽  
Interleukin 4 ◽  
Polymorphonuclear Cells ◽  
Helicobacter Hepaticus ◽  
Igg2a Antibody ◽  
Ifn Γ ◽  
Th1 Immune Response

ABSTRACT Helicobacter hepaticus infection in A/JCr mice results in chronic active hepatitis characterized by perivascular, periportal, and parenchymal infiltrates of mononuclear and polymorphonuclear cells. This study examined the development of hepatitis and the immune response of A/JCr mice to H. hepaticus infection. The humoral and cell-mediated T helper immune response was profiled by measuring the postinfection (p.i.) antibody response in serum, feces, and bile and by the production of cytokines and proliferative responses by splenic mononuclear cells to H. hepaticusantigens. Secretory immunoglobulin A (IgA) and systemic IgG2a antibody developed by 4 weeks p.i. and persisted through 12 months. Splenocytes from infected mice proliferated and produced more gamma interferon (IFN-γ) than interleukin-4 (IL-4) or IL-5 when cultured with H. hepaticus outer membrane proteins. The predominantly IgG2a antibody response in serum and the in vitro production of IFN-γ in excess of IL-4 or IL-5 are consistent with a Th1 immune response reported in humans and mice infected withHelicobacter pylori and Helicobacter felis, respectively. Mice infected with H. hepaticus developed progressively severe perivascular, periportal, and hepatic parenchymal lesions consisting of lymphohistiocytic and plasmacytic cellular infiltrates. In addition, transmural typhlitis was observed at 12 months p.i. The characterization of a cell-mediated Th1 immune response toH. hepaticus infection in the A/JCr mouse should prove valuable as a model for experimental regimens which manipulate the host response to Helicobacter.

scholarly journals Kinetics of Phenotypic and Functional Changes in Mouse Models of Sponge Implants: Rational Selection to Optimize Protocols for Specific Biomolecules Screening Purposes

2020 ◽  
Vol 8 ◽  
Author(s):  
Mariana Ferreira Lanna ◽  
Lucilene Aparecida Resende ◽  
Rodrigo Dian de Oliveira Aguiar-Soares ◽  
Marina Barcelos de Miranda ◽  
Ludmila Zanandreis de Mendonça ◽  
...  
Keyword(s):  
Immune Response ◽  
Cytokine Production ◽  
Late Time ◽  
Polymorphonuclear Cells ◽  
Rational Selection ◽  
Matrix Deposition ◽  
Functional Features ◽  
Ifn Γ ◽  
Selection Of ◽  
Time Point

The sponge implant has been applied as an important in vivo model for the study of inflammatory processes as it induces the migration, proliferation, and accumulation of inflammatory cells, angiogenesis, and extracellular matrix deposition in its trabeculae. The characterization of immune events in sponge implants would be useful in identifying the immunological events that could support the selection of an appropriate experimental model (mouse strain) and time post-implant analysis in optimized protocols for novel applications of this model such as in biomolecules screening. Here, the changes in histological/morphometric, immunophenotypic and functional features of infiltrating leukocytes (LEU) were assessed in sponge implants for Swiss, BALB/c, and C57BL/6 mice. A gradual increase of fibrovascular stroma and a progressive decrease in LEU infiltration, mainly composed of polymorphonuclear cells with progressive shift toward mononuclear cells at late time-points were observed over time. Usually, Swiss mice presented a more prominent immune response with late mixed pattern (pro-inflammatory/anti-inflammatory: IL-2/IFN-γ/IL-4/IL-10/IL-17) of cytokine production. While BALB/c mice showed an early activation of the innate response with a controlled cytokine profile (low inflammatory potential), C57BL/6 mice presented a typical early pro-inflammatory (IL-6/TNF/IFN-γ) response with persistent neutrophilic involvement. A rational selection of the ideal time-point/mouse-lineage would avoid bias or tendentious results. Criteria such as low number of increased biomarkers, no recruitment of cytotoxic response, minor cytokine production, and lower biomarker connectivity (described as biomarker signature analysis and network analysis) guided the choice of the best time-point for each model (Day5/Swiss; Day7/BALB/c; Day6/C57BL/6) with wide application for screening purposes, such as identification of therapeutic biomolecules, selection of antigens/adjuvants, and follow-up of innate and adaptive immune response to vaccines candidates.

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 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 Intraspleen Delivery of a DNA Vaccine Coding for Superoxide Dismutase (SOD) of Brucella abortus Induces SOD-Specific CD4+ and CD8+ T Cells

2004 ◽  
Vol 72 (4) ◽  
pp. 2081-2087 ◽  
Author(s):  
Carola Muñoz-Montesino ◽  
Edilia Andrews ◽  
Rodolfo Rivers ◽  
Andrés González-Smith ◽  
Gustavo Moraga-Cid ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Superoxide Dismutase ◽  
T Cell ◽  
Cytotoxic Activity ◽  
Brucella Abortus ◽  
Plasmid Dna ◽  
Interleukin 4 ◽  
Similar Amount ◽  
Ifn Γ

ABSTRACT In the development of vaccines capable of providing immunity against brucellosis, Cu-Zn superoxide dismutase (SOD) has been demonstrated to be one of the protective immunogens of Brucella abortus. In an earlier study, we provided strong evidence that intramuscular injection with a plasmid DNA carrying the SOD gene (pcDNA-SOD) was able to induce a protective immune response. The present study was designed to characterize T-cell immune responses after an intraspleen (i.s.) vaccination of BALB/c mice with pcDNA-SOD. Animals vaccinated with pcDNA-SOD did not develop SOD-specific antibodies, at least until week 4 after immunization (the end of the experiment), and in vitro stimulation of their splenocytes with either recombinant Cu-Zn SOD or crude Brucella protein induced the secretion of gamma interferon (IFN-γ), but not interleukin-4, and elicited the induction of cytotoxic-T-lymphocyte activity. Upon analyzing the SOD-specific T-cell responses, the pcDNA-SOD vaccination was found to be stimulating both CD4+- and CD8+-T-cell populations. However, only the CD4+ population was able to produce IFN-γ and only the CD8+ population was able to induce cytotoxic activity. Nevertheless, although i.s. route vaccination induces a significant level of protection in BALB/c mice against challenge with the virulent B. abortus strain 2308, vaccination by the intramuscular route with a similar amount of plasmid DNA does not protect. Based on these results, we conclude that i.s. immunization with pcDNA-SOD vaccine efficiently induced a Th1 type of immune response and a protective response that could be related to IFN-γ production and cytotoxic activity against infected cells by SOD-specific CD4+ and CD8+ T cells, respectively.

scholarly journals Cytokine Profiles of Patients Infected with Mycobacterium ulcerans and Unaffected Household Contacts

2002 ◽  
Vol 70 (10) ◽  
pp. 5562-5567 ◽  
Author(s):  
Travis M. Gooding ◽  
Paul D. R. Johnson ◽  
May Smith ◽  
Andrew S. Kemp ◽  
Roy M. Robins-Browne
Keyword(s):  
Immune Response ◽  
Mononuclear Cells ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Interleukin 4 ◽  
Peripheral Blood Mononuclear ◽  
Household Contacts ◽  
Control Subjects ◽  
Cytokine Profiles ◽  
Ifn Γ

ABSTRACT Mycobacterium ulcerans, the cause of Buruli ulcer, is an environmental mycobacterium with a distinct geographic distribution. The reasons why only some individuals who are exposed to M. ulcerans develop ulcers are not known but are likely to reflect individual differences in the immune response to infections with this bacterium. In this study, we investigated cytokine profiles of peripheral blood mononuclear cells (PBMC) from 23 Buruli ulcer patients and 25 household contacts in a region of Australia where Buruli ulcer is endemic. The results showed that following stimulation with M. ulcerans or Mycobacterium bovis BCG, PBMC from Buruli ulcer patients mounted a Th2-type response, which was manifested by the production of mRNA for interleukin 4 (IL-4), IL-5, IL-6, and IL-10, whereas unaffected contacts responded mainly with the Th1 cytokines gamma interferon (IFN-γ) and IL-12. For example, mRNA for IL-4 was detected in 18 of 23 patients but in only 3 of 25 control subjects (P < 0.0001). By contrast, PBMC from 21 of 25 unaffected individuals produced IFN-γ compared with 3 of 23 patients (P < 0.0001). IFN-γ release following stimulation with mycobacteria was markedly reduced in affected subjects. Frequencies of antibodies to M. ulcerans in serum samples from affected and unaffected subjects were similar, indicating that many of the control subjects had been exposed to this bacterium. Together, these findings suggest that a Th1-type immune response to M. ulcerans may prevent the development of Buruli ulcer in people exposed to M. ulcerans, but a Th-2 response does not.

scholarly journals Peripheral Cytokine Responses to Trichuris muris Reflect Those Occurring Locally at the Site of Infection

2000 ◽  
Vol 68 (4) ◽  
pp. 1815-1819 ◽  
Author(s):  
Matthew D. Taylor ◽  
Catherine J. Betts ◽  
Kathryn J. Else
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Peripheral Blood ◽  
Cytokine Response ◽  
Interleukin 4 ◽  
Intestinal Helminth ◽  
Trichuris Muris ◽  
Cytokine Responses ◽  
Ifn Γ

ABSTRACT The study of human cellular immune responses to parasite infection under field conditions is very complex. Often, the only practical site from which to sample the cellular responses is the peripheral blood. Sampling peripheral blood lymphocytes (PBL) relies on the assumption that these peripheral responses accurately reflect the immune responses acting locally at the site of infection. This is a particularly important point for the human intestinal helminth Trichuris trichiura, which solely inhabits the cecum and large intestine and so will stimulate a localized immune response. Using the well-defined model of T. trichiura, T. muris in the mouse, we have demonstrated that the dominant cytokine responses of the mesenteric lymph nodes (MLN) can be detected by sampling PBL. Resistant mice which mount a type 2 cytokine response in their MLN had PBL producing interleukin-4 (IL-4), IL-5, and IL-9, with negligible levels of gamma interferon (IFN-γ). Conversely, susceptible mice which mount a type 1 cytokine response in their MLN had PBL producing IFN-γ and negligible levels of type 2 cytokines. We have also shown that the PBL are capable of mounting a functional immune response against T. muris. PBL from immune mice were capable of transferring immunity to T. muris-infected severe combined immunodeficient (C.B-17 scid/scid) mice. Sampling PBL responses is therefore a viable option for monitoring human intestinal immune responses during T. trichiura infection in the field.

scholarly journals Immune Response to Haemophilus parainfluenzae in Patients with Chronic Obstructive Lung Disease

2000 ◽  
Vol 7 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Joanne L. Mitchell ◽  
Susan L. Hill
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Lung Disease ◽  
Obstructive Lung Disease ◽  
Outer Membrane Proteins ◽  
Chronic Obstructive Lung Disease ◽  
Chronic Obstructive ◽  
Antigen Specificity ◽  
Serum Samples ◽  
Haemophilus Parainfluenzae

ABSTRACT Haemophilus parainfluenzae is often isolated from the sputa of patients with chronic obstructive lung disease. We have investigated the immune response to this organism in patients with chronic bronchitis (n = 3) and bronchiectasis (n = 10) and in healthy controls (n = 9). Outer membrane proteins (OMPs) of H. parainfluenzaewere purified for use in enzyme-linked immunosorbent and immunoblot assays. Whole-cell H. parainfluenzae preparations were used to adsorb antibodies from serum samples, which were subsequently immunoblot assayed to investigate the antibody response to surface-exposed epitopes. Levels of H. parainfluenzae-specific immunoglobulin G (IgG), but not IgA or IgM, were increased in the sera of patients with chronic obstructive lung disease compared to levels in control subjects. The species specificity of the antibody response was confirmed, although a degree of cross-reactivity with H. influenzae antigens was observed. IgA and IgG specific for OMPs of H. parainfluenzae were demonstrated to be present in the sputa and sera of five patients with chronic obstructive lung disease. Variation in the pattern and intensity of antigen recognition was observed among patients and among immunoglobulin classes. OMPs of approximately 36, 22, and 15 kDa were confirmed to possess epitopes exposed on the surface of intact H. parainfluenzae. We have demonstrated the presence of a species-specific systemic immune response to H. parainfluenzae in colonized patients. A specific antibody response was also observed in sputum, and the antigen specificity of these responses in patients with chronic obstructive lung disease was investigated for the first time. The presence of a specific immune response suggests that H. parainfluenzae may have a pathogenic role in patients with chronic obstructive lung disease.

scholarly journals Immunization with Brucella VirB Proteins Reduces Organ Colonization in Mice through a Th1-Type Immune Response and Elicits a Similar Immune Response in Dogs

2014 ◽  
Vol 22 (3) ◽  
pp. 274-281 ◽  
Author(s):  
Cora N. Pollak ◽  
María Magdalena Wanke ◽  
Silvia M. Estein ◽  
M. Victoria Delpino ◽  
Norma E. Monachesi ◽  
...  
Keyword(s):  
Immune Response ◽  
Mononuclear Cells ◽  
Interleukin 4 ◽  
Delayed Type Hypersensitivity ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Type Iv ◽  
Ifn Γ ◽  
Organ Colonization

ABSTRACTVirB proteins fromBrucellaspp. constitute the type IV secretion system, a key virulence factor mediating the intracellular survival of these bacteria. Here, we assessed whether a Th1-type immune response against VirB proteins may protect mice fromBrucellainfection and whether this response can be induced in the dog, a natural host forBrucella. Splenocytes from mice immunized with VirB7 or VirB9 responded to their respective antigens with significant and specific production of gamma interferon (IFN-γ), whereas interleukin-4 (IL-4) was not detected. Thirty days after an intraperitoneal challenge with liveBrucella abortus, the spleen load of bacteria was almost 1 log lower in mice immunized with VirB proteins than in unvaccinated animals. As colonization reduction seemed to correlate with a Th1-type immune response against VirB proteins, we decided to assess whether such a response could be elicited in the dog. Peripheral blood mononuclear cells (PBMCs) from dogs immunized with VirB proteins (three subcutaneous doses in QuilA adjuvant) produced significantly higher levels of IFN-γ than cells from control animals uponin vitrostimulation with VirB proteins. A skin test to assess specific delayed-type hypersensitivity was positive in 4 out of 5 dogs immunized with either VirB7 or VirB9. As both proteins are predicted to locate in the outer membrane ofBrucellaorganisms, the ability of anti-VirB antibodies to mediate complement-dependent bacteriolysis ofB. caniswas assessedin vitro. Sera from dogs immunized with either VirB7 or VirB9, but not from those receiving phosphate-buffered saline (PBS), produced significant bacteriolysis. These results suggest that VirB-specific responses that reduce organ colonization byBrucellain mice can be also elicited in dogs.

scholarly journals The Th1 Immune Response to Plasmodium falciparum Circumsporozoite Protein Is Boosted by Adenovirus Vectors 35 and 26 with a Homologous Insert

2010 ◽  
Vol 17 (11) ◽  
pp. 1687-1694 ◽  
Author(s):  
Katarina Radošević ◽  
Ariane Rodriguez ◽  
Angelique A. C. Lemckert ◽  
Marjolein van der Meer ◽  
Gert Gillissen ◽  
...  
Keyword(s):  
Immune Response ◽  
Plasmodium Falciparum ◽  
T Cell ◽  
Cell Response ◽  
T Cell Responses ◽  
T Cell Response ◽  
Virus Surface ◽  
Cell Responses ◽  
Ifn Γ ◽  
Th1 Immune Response

ABSTRACT The most advanced malaria vaccine, RTS,S, is comprised of an adjuvant portion of the Plasmodium falciparum circumsporozoite (CS) protein fused to and admixed with the hepatitis B virus surface antigen. This vaccine confers short-term protection against malaria infection, with an efficacy of about 50%, and induces particularly B-cell and CD4+ T-cell responses. In the present study, we tested by the hypothesis that the Th1 immune response to CS protein, in particular the CD8+ T-cell response, which is needed for strong and lasting malaria immunity, is boosted to sustainable levels vectors adenovirus and 26 with an homologous insert 35 (Ad35.CS/Ad26.CS). In this study, we evaluated immune responses induced with vaccination regimens based on an adjuvant-containing, yeast-produced complete CS protein followed by two recombinant low-seroprevalence adenoviruses expressing P. falciparum CS antigen, Ad35.CS (subgroup B) and Ad26.CS (subgroup D). Our results show that (i) the yeast (Hansenula polymorpha)produced, adjuvanted full-length CS protein is highly potent in inducing high CS-specific humoral responses in mice but produces poor T-cell responses, (ii) the Ad35.CS vector boosts the gamma interferon-positive (IFN-γ+) CD8+ T-cell response induced by the CS protein immunization and shifts the immune response toward the Th1 type, and (iii) a three-component heterologous vaccination comprised of a CS protein prime followed by boosts with Ad35.CS and Ad26.CS elicits an even more robust and sustainable IFN-γ+ CD8+ T-cell response than one- or two-component regimens. The Ad35.CS/Ad26.CS combination boosted particularly the IFN-γ+ and tumor necrosis factor alpha-positive (TNF-α+) T cells, confirming the shift of the immune response from the Th2 type to the Th1 type. These results support the notion of first immunizations of infants with an adjuvanted CS protein vaccine, followed by a booster Ad35.CS/Ad26.CS vaccine at a later age, to induce lasting protection against malaria for which the Th1 response and immune memory is required.

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