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 Evaluation of Immunostimulatory Activities of Synthetic Mannose-Containing Structures Mimicking the β-(1→2)-Linked Cell Wall Mannans of Candida albicans

2012 ◽  
Vol 19 (11) ◽  
pp. 1889-1893 ◽  
Author(s):  
Kaarina Ranta ◽  
Kaisa Nieminen ◽  
Filip S. Ekholm ◽  
Moniká Poláková ◽  
Mattias U. Roslund ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Mouse Macrophages ◽  
Ifn Γ ◽  
Low Levels ◽  
Necrosis Factor

ABSTRACTImmunostimulatory properties of synthetic structures mimicking the β-(1→2)-linked mannans ofCandida albicanswere evaluatedin vitro. Contrary to earlier observations, tumor necrosis factor (TNF) production was not detected after stimulation with mannotetraose in mouse macrophages. Divalent disaccharide 1,4-bis(α-d-mannopyranosyloxy)butane induced TNF and some molecules induced low levels of gamma interferon (IFN-γ) in human peripheral blood mononuclear cells (PBMC).

scholarly journals Spontaneous secretion of interferon γ and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes

Gut ◽  
1998 ◽  
Vol 42 (5) ◽  
pp. 643-649 ◽  
Author(s):  
M Carol ◽  
A Lambrechts ◽  
A Van Gossum ◽  
M Libin ◽  
M Goldman ◽  
...  
Keyword(s):  
Lamina Propria ◽  
Intestinal Mucosa ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Gastrointestinal Diseases ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

Background—Cytokines secreted by intestinal T lymphocytes probably play a critical role in regulation of the gut associated immune responses.Aims—To quantify interferon γ (IFN-γ) and interleukin 4 (IL-4) secreting cells (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from the duodenum and right colon in non-pathological situations and in the absence of in vitro stimulation.Patients—Duodenal and right colonic biopsy specimens were obtained from patients with no inflammation of the intestinal mucosa.Methods—Intraepithelial and lamina propria cell suspensions were assayed for numbers of cells spontaneously secreting IFN-γ and IL-4 by a two site reverse enzyme linked immunospot technique (ELISPOT).Results—The relatively high proportion of duodenal lymphocytes spontaneously secreting IFN-γ (IEL 3.6%; LPL 1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously IFN-γ SC and the absence of spontaneously IL-4 SC among peripheral blood mononuclear cells. In the basal state, both IFN-γ and IL-4 were mainly produced by CD4+ cells. Within the colon, only 0.2% of IEL and LPL secreted IFN-γ in the basal state, and 0.1% secreted IL-4.Conclusions—Compared with peripheral lymphocytes substantial proportions of intestinal epithelial and lamina propria lymphocytes spontaneously secrete IFN-γ and/or IL-4. These cytokines are probably involved in the normal homoeostasis of the human intestinal mucosa. Disturbances in their secretion could play a role in the pathogenesis of gastrointestinal diseases.

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 Protective and Pathological Functions of CD8+T Cells in Leishmania braziliensis Infection

2014 ◽  
Vol 83 (3) ◽  
pp. 898-906 ◽  
Author(s):  
Thiago Marconi Cardoso ◽  
Álvaro Machado ◽  
Diego Luiz Costa ◽  
Lucas P. Carvalho ◽  
Adriano Queiroz ◽  
...  
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Granzyme B ◽  
Delayed Type Hypersensitivity ◽  
Leishmania Braziliensis ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Factor Alpha ◽  
Ifn Γ

Cutaneous leishmaniasis (CL) caused byLeishmania braziliensisis characterized by a strong Th1 response that leads to skin lesion development. In areas whereL. braziliensistransmission is endemic, up to 15% of healthy subjects have tested positive for delayed-type hypersensitivity to soluble leishmania antigen (SLA) and are considered to have subclinical (SC) infection. SC subjects produce less gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) than do CL patients, but they are able to control the infection. The aim of this study was to characterized the role of CD8+T cells in SC infection and in CL. Peripheral blood mononuclear cells (PBMC) were stimulated with SLA to determine the frequencies of CD4+IFN-γ+and CD8+IFN-γ+T cells. Monocytes from PBMC were infected withL. braziliensisand cocultured with CD8+T cells, and the frequencies of infected monocytes and levels of cytotoxicity markers, target cell apoptosis, and granzyme B were determined. The frequency of CD8+IFN-γ+cells after SLA stimulation was higher for SC individuals than for CL patients. The frequency of infected monocytes in SC cells was lower than that in CL cells. CL CD8+T cells induced more apoptosis of infected monocytes than did SC CD8+T cells. Granzyme B production in CD8+T cells was higher in CL than in SC cells. While the use of a granzyme B inhibitor decreased the number of apoptotic cells in the CL group, the use of z-VAD-FMK had no effect on the frequency of these cells. These results suggest that CL CD8+T cells are more cytotoxic and may be involved in pathology.

scholarly journals Immune Responses in Cutaneous Leishmaniasis: in vitro Thelper1/Thelper2 Cy-tokine Profiles Using Live Versus Killed Leishmania major

2021 ◽  
Author(s):  
Akram Miramin-Mohammadi ◽  
Amir Javadi ◽  
Seyyed Ebrahim Eskandari ◽  
Mahmood Nateghi-Rostami ◽  
Ali Khamesipour
Keyword(s):  
Immune Response ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Mononuclear Cells ◽  
Control Measure ◽  
Peripheral Blood Mononuclear ◽  
Significant Difference ◽  
History Of ◽  
Ifn Γ

Background: Recovery from cutaneous leishmaniasis (CL) leads to protection against further lesion development. In contrast, vaccination using killed parasites does not induce enough protection; the reason(s) is not currently known but might be related to different immune response induced against live versus killed parasites. In this study, Th1/Th2 cyto-kine profiles of CL patients were evaluated against live versus killed Leishmania major. Methods: In this study peripheral blood mononuclear cells (PBMC) of the volunteers with active CL lesion (CL), history of CL (HCL) and healthy volunteers were cultured and stimulated with live or killed Leishmania major, the superna-tants were collected and levels of IFN-γ, IL-5 and IL-10 were titrated using ELISA method. Results: The results showed that IFN-γ levels in CL patients (p< 0.001) and HCL volunteers (p< 0.005) are signifi-cantly higher when stimulated with live than stimulated with killed L. major. IFN-γ production in PBMC volunteers with CL and HCL stimulated with live or heat-killed L. major was significantly (p< 0.001) higher than in unstimulated ones. The level of IL-5 in CL patients (p< 0.005) and HCL volunteers (p< 0.001) are significantly lower when stimulated with live than killed L. major. There was no significant difference between the levels of IL-10 in PBMC stimulated with either live or killed L. major. Conclusion: It is concluded that using live Leishmania induces a stronger Th1 type of immune response which justify using leishmanization as a control measure against CL.

scholarly journals Heterogeneity of Wild Leishmania major Isolates in Experimental Murine Pathogenicity and Specific Immune Response

2001 ◽  
Vol 69 (8) ◽  
pp. 4906-4915 ◽  
Author(s):  
C. Kébaı̈er ◽  
H. Louzir ◽  
M. Chenik ◽  
A. Ben Salah ◽  
K. Dellagi
Keyword(s):  
Immune Response ◽  
Lymph Node ◽  
Leishmania Major ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Interleukin 4 ◽  
Zoonotic Cutaneous Leishmaniasis ◽  
Tunisian Patients ◽  
Ifn Γ

ABSTRACT Virulence variability was investigated by analyzing the experimental pathogenicity of 19 Leishmania major strains in susceptible BALB/c mice. Twelve strains were isolated from Tunisian patients with zoonotic cutaneous leishmaniasis; seven strains were isolated in Syria (n = 1), Saudi Arabia (n = 2), Jordan (n = 2), or Israel (n = 2). BALB/c mice were injected in the hind footpad with 2 × 106 amastigotes of the various isolates, and lesion progression was recorded weekly for 9 weeks. Interleukin-4 (IL-4) and gamma interferon (IFN-γ) production of lymph node mononuclear cells activated in vitro with parasite antigens were evaluated 5 weeks after infection. We show that disease progression induced by different L. major isolates was largely heterogeneous although reproducible results were obtained when using the same isolate. Interestingly, isolates from the Middle East induced a more severe disease than did the majority of Tunisian isolates. Strains with the highest virulence tend to generate more IL-4 and less IFN-γ in vitro at week 5 postinfection as well as higher levels of early IL-4 mRNA in the lymph node draining the inoculation site at 16 h postinfection. These results suggest that L. major isolates from the field may differ in virulence, which influences the course of the disease induced in mice and the type of immune response elicited by the infected host.

scholarly journals Immune Responses of Bison and Efficacy after Booster Vaccination with Brucella abortus Strain RB51

2015 ◽  
Vol 22 (4) ◽  
pp. 440-447 ◽  
Author(s):  
S. C. Olsen ◽  
J. L. McGill ◽  
R. E. Sacco ◽  
S. G. Hennager
Keyword(s):  
Brucella Abortus ◽  
Mononuclear Cells ◽  
Herd Immunity ◽  
Vaccination Strategy ◽  
Booster Vaccination ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Single Vaccination ◽  
Ifn Γ

ABSTRACTThirty-one bison heifers were randomly assigned to receive saline or a single vaccination with 1010CFU ofBrucella abortusstrain RB51. Some vaccinated bison were randomly selected for booster vaccination with RB51 at 11 months after the initial vaccination. Mean antibody responses to RB51 were greater (P< 0.05) in vaccinated bison after initial and booster vaccination than in nonvaccinated bison. The proliferative responses by peripheral blood mononuclear cells (PBMC) from the vaccinated bison were greater (P< 0.05) than those in the nonvaccinated bison at 16 and 24 weeks after the initial vaccination but not after the booster vaccination. The relative gene expression of gamma interferon (IFN-γ) was increased (P< 0.05) in the RB51-vaccinated bison at 8, 16, and 24 weeks after the initial vaccination and at 8 weeks after the booster vaccination. The vaccinated bison had greater (P< 0.05)in vitroproduction of IFN-γ at all sampling times, greater interleukin-1β (IL-1β) production in various samplings after the initial and booster vaccinations, and greater IL-6 production at one sampling time after the booster vaccination. Between 170 and 180 days of gestation, the bison were intraconjunctivally challenged with approximately 1 × 107CFU ofB. abortusstrain 2308. The incidences of abortion and infection were greater (P< 0.05) in the nonvaccinated bison after experimental challenge than in the bison receiving either vaccination treatment. Booster-vaccinated, but not single-vaccinated bison, had a reduced (P< 0.05) incidence of infection in fetal tissues and maternal tissues compared to that in the controls. Compared to the nonvaccinated bison, both vaccination treatments lowered the colonization (measured as the CFU/g of tissue) ofBrucellaorganisms in all tissues, except in retropharyngeal and supramammary lymph nodes. Our study suggests that RB51 booster vaccination is an effective vaccination strategy for enhancing herd immunity against brucellosis in bison.

scholarly journals Effect of Pasteurella multocida Soluble Antigen Stimulation on the In Vitro Response of Peripheral Blood Mononuclear Cells of Holstein Calves

2018 ◽  
Vol 68 (2) ◽  
pp. 201-210
Author(s):  
Hiromichi Ohtsuka ◽  
Maki Inoue ◽  
Yosuke Maeda ◽  
Taishi Tanabe ◽  
Motoshi Tajima
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 4 ◽  
Soluble Antigen ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Holstein Calves ◽  
Ifn Γ

Abstract The expressions of cytokines mRNA, including interleukin-4 (IL-4), interleukin- 17A (IL-17A) and interferon-gamma (IFN-γ), their master regulatory transcription factors, and signal transducers and activator of transcription (STAT) stimulated in vitro with Pasteurella (P.) multocida soluble antigen were examined in peripheral blood mononuclear cells (PBMC) from Holstein calves. The healthy Holstein calves were divided into three groups; 2 weeks old (2W Group, N=8), 6 weeks old (6W Group, N=8), and 10 weeks old (10W Group, N=8). PBMC were stimulated in vitro by soluble antigen of P. multocida. There were significantly lower expressions of IFN-γ, IL-4, and STAT-6 mRNA of PBMC stimulated with P. multocida soluble antigen in the 2W Group compared to that in the 10W Group. Expression of IL-17A and IFN-γ in PBMC stimulated with P. multocida soluble antigen were significantly higher compared with the PBMC without stimulation in the 6W groups. The results of the present study demonstrated that 2W old calves had decreased cytokine expression of PBMC when in vitro stimulated with P. multocida soluble antigen in vitro.

scholarly journals Immune Response Induction and New Effector Mechanisms Possibly Involved in Protection Conferred by the Cuban Anti-Meningococcal BC Vaccine

2001 ◽  
Vol 69 (7) ◽  
pp. 4502-4508 ◽  
Author(s):  
Oliver Pérez ◽  
Miriam Lastre ◽  
José Lapinet ◽  
Gustavo Bracho ◽  
Miriam Dı́az ◽  
...  
Keyword(s):  
Immune Response ◽  
Mononuclear Cells ◽  
Adult Population ◽  
Interleukin 2 ◽  
Outer Membrane Vesicles ◽  
Delayed Type Hypersensitivity ◽  
T Helper 1 ◽  
Opsonic Activity ◽  
Peripheral Blood Mononuclear

ABSTRACT This report explores the participation of some afferent mechanisms in the immune response induced by the Cuban anti-meningococcal vaccine VA-MENGOC-BC. The induction of delayed-type hypersensitivity in nursing babies and lymphocyte proliferation after immunization is demonstrated. The presence of gamma interferon IFN-γ and interleukin-2 (IL-2) mRNAs but absence of IL-4, IL-5, and IL-10 mRNAs were observed in peripheral blood mononuclear cells from immunized subjects after in vitro challenge with outer membrane vesicles. In addition, some effector functions were also explored. The presence of opsonic activity was demonstrated in sera from vaccinees. The role of neutrophils as essential effector cells was shown. In conclusion, we have shown that, at least in the Cuban adult population, VA-MENGOC-BC induces mechanisms with a T-helper 1 pattern in the afferent and effector branches of the immune response.

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