scholarly journals Differential Immune Response against RecombinantLeishmania donovaniPeroxidoxin 1 and Peroxidoxin 2 Proteins in BALB/c Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Nada S. Daifalla ◽  
Abebe Genetu Bayih ◽  
Lashitew Gedamu
Keyword(s):  
Immune Response ◽  
Leishmania Donovani ◽  
Cpg Odn ◽  
Spleen Cells ◽  
Th2 Response ◽  
Tlr Agonists ◽  
Igg2a Isotype ◽  
High Level ◽  
Th 1 ◽  
Igg1 Isotype

We assessed the immune response against recombinant proteins of two related, albeit functionally different, peroxidoxins fromLeishmania donovani: peroxidoxin 1 (LdPxn1) and peroxidoxin 2 (LdPxn2) in BALB/c mice. We also evaluated the effect of coadministration of TLR agonists (CpG ODN and GLA-SE) on the antigen-specific immune response. Immunization with recombinant LdPxn1 alone induced a predominantly Th2 type immune response that is associated with the production of high level of IgG1 and no IgG2a isotype while rLdPxn2 resulted in a mixed Th1/Th2 response characterized by the production of antigen-specific IgG2a in addition to IgG1 isotype. Antigen-stimulated spleen cells from mice that were immunized with rLdPxn1 produced low level of IL-10 and IL-4 and no IFN-γ, whereas cells from mice immunized with rLdPxn2 secreted high level of IFN-γ, low IL-4, and no IL-10. Coadministration of CpG ODN or GLA-SE with rLdPxn1 skewed the immune response towards a Th 1 type as indicated by robust production of IgG2a isotype. Furthermore, the presence of TLR agonists together with rLdPxn1 antigen enhanced the production of IFN-γand to a lesser extent of IL-10. TLR agonists also enhanced a more polarized Th 1 type immune response against rLdPxn2.

scholarly journals Immune Response and Protective Efficacy of a Heterologous DNA-Protein Immunization withLeishmaniaSuperoxide Dismutase B1

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Abebe Genetu Bayih ◽  
Nada S. Daifalla ◽  
Lashitew Gedamu
Keyword(s):  
Immune Response ◽  
Mammalian Cells ◽  
Leishmania Donovani ◽  
Protective Efficacy ◽  
Vaccine Antigen ◽  
High Dose ◽  
Spleen Cells ◽  
Th2 Response ◽  
Flow Cytometry Data ◽  
Multiparametric Flow Cytometry

Growing evidence shows that antioxidant proteins ofLeishmaniacould be used as vaccine candidates. In this study, we report the efficacy ofLeishmania donovaniiron superoxide dismutase B1 (LdFeSODB1) as a vaccine antigen in BALB/c mice in a DNA-protein prime-boost immunization regimen in the presence or absence of murine granulocyte macrophage colony stimulating factor (mGMCSF) DNA adjuvant. The expression study confirmed that LdFeSODB1 is expressed in mammalian cells and mGMCSF fusion mediates the secretion of the recombinant protein. Heterologous immunization with LdFeSODB1 induced a strong antibody- and cell-mediated immune response in mice. Immunization triggered a mixed Th1/Th2 response as evidenced by the ratio of IgG2a to IgG1. Antigen-stimulated spleen cells from the immunized mice produced high level IFN-γ. Multiparametric flow cytometry data showed that immunization with LdFeSODB1 induced significantly higher expression of TNF-αor IL-2 by antigen-stimulated T cells. Eight weeks afterL. majorinfection, immunization with the antigen shifted the immune response to a more Th1 type than the controls as demonstrated by IgG2a/IgG1 ratio. Moreover, IFN-γproduction by antigen-stimulated spleen cells from immunized mice remained high. The footpad swelling experiment showed that immunization with LdFeSODB1 resulted in partial protection of mice from a high doseL. majorinfection.

scholarly journals The IL-33/ST2 Axis Is Associated with Human Visceral Leishmaniasis and Suppresses Th1 Responses in the Livers of BALB/c Mice Infected with Leishmania donovani

mBio ◽  
2013 ◽  
Vol 4 (5) ◽  
Author(s):  
Octavie Rostan ◽  
Jean-Pierre Gangneux ◽  
Claire Piquet-Pellorce ◽  
Christelle Manuel ◽  
Andrew N. J. McKenzie ◽  
...  
Keyword(s):  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Parasite Burden ◽  
World Health ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cytokine Signaling ◽  
Th2 Response ◽  
Content Type ◽  
Th1 Cytokines

ABSTRACT During visceral leishmaniasis, the control of hepatic parasite burden is mainly due to granuloma assembly in a microenvironment consisting of both Th1 and Th2 components. Using enzyme-linked immunosorbent assay (ELISA) dosages, quantitative PCR (qPCR), immunohistochemistry, and flow cytometry, we studied the role of interleukin-33 (IL-33), a recently described cytokine signaling through the ST2 receptor, during visceral leishmaniasis. We showed that a higher level of IL-33 was detected in the serum of patients with visceral leishmaniasis than in that from healthy donors and demonstrated the presence of IL-33+ cells in a liver biopsy specimen from a patient. Similarly, in BALB/c mice experimentally infected with L. donovani, a higher level of IL-33 was detected in the serum, as well as the presence of IL-33+ cells and ST2+ cells in the mouse liver. In ST2−/− BALB/c mice, better control of the hepatic parasite burden and reduced hepatomegaly were observed. This was associated with strong induction of Th1 cytokines (gamma interferon [IFN-γ] and IL-12) compared to the level in wild-type (WT) mice and better recruitment of myeloid cells associated with strongly induced chemokines (CCL2 and CXCL2) and receptors (CCR2 and CXCR2). Conversely, BALB/c mice treated twice weekly with recombinant IL-33 showed a dramatically reduced induction of Th1 cytokines and delayed inhibition of monocyte and neutrophil recruitment in the liver, which was associated with reduced KC/CXCL1 and CXCR2 expression. Taken together, our results suggest that IL-33 could be a new deleterious regulator of the hepatic immune response against Leishmania donovani, via the repression of the Th1 response and myeloid cell recruitment. IMPORTANCE Visceral leishmaniasis is a life-threatening systemic disease due to the Leishmania protozoa L. infantum and L. donovani and is ranked by the World Health Organization as the second most important protozoan parasitic disease after malaria for its grave morbidity, high mortality, and global distribution. Leishmania parasites subvert the host’s immune response to propagate to target organs, including the spleen, the bone marrow, and the liver. Control of hepatic parasite burdens depends on a delicate and poorly understood Th1/Th2 immune balance. To better understand this complex immune response, new cytokines are interesting targets for research studies. IL-33 is a newly described cytokine usually associated with Th2 response and involved in different diseases, including infectious diseases and hepatitis. Our results suggest that IL-33 could be a new factor of susceptibility and a potential prognostic marker during visceral leishmaniasis.

scholarly journals Repeated Administration of Synthetic Oligodeoxynucleotides Expressing CpG Motifs Provides Long-Term Protection against Bacterial Infection

1999 ◽  
Vol 67 (11) ◽  
pp. 5658-5663 ◽  
Author(s):  
Dennis M. Klinman ◽  
Jackie Conover ◽  
Cevahir Coban
Keyword(s):  
Immune Response ◽  
Repeated Administration ◽  
Immunoglobulin M ◽  
Innate Immune ◽  
Cpg Odn ◽  
Spleen Cells ◽  
Cpg Motifs ◽  
Pathogen Exposure

ABSTRACT Synthetic oligodeoxynucleotides (ODN) expressing unmethylated CpG motifs stimulate an innate immune response characterized by the production of polyreactive immunoglobulin M antibodies and immunomodulatory cytokines. This immune response has been shown to protect mice from challenge by Listeria monocytogenes andFrancisella tularensis for up to 2 weeks. By repeatedly administering CpG ODN two to four times/month, we found that this protection could be maintained indefinitely. Protection was associated with a significant increase in the number of spleen cells that could be triggered by subsequent pathogen exposure to secrete gamma interferon and interleukin-6 in vivo (P < 0.01). ODN-treated animals remained healthy and developed neither macroscopic nor microscopic evidence of tissue damage or inflammation. Thus, repeated administration of CpG ODN may provide a safe means of conferring long-term protection against infectious pathogens.

scholarly journals Coupled complementation of immune response genes controlling responsiveness to the H-2.2 alloantigen.

1977 ◽  
Vol 146 (2) ◽  
pp. 571-578 ◽  
Author(s):  
M E Dorf ◽  
J H Stimpfling
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Humoral Response ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
F1 Hybrids ◽  
Gene Control ◽  
Low Responder ◽  
Resistant Strains ◽  
High Level

The ability of various B10 congenic resistant strains to respond to the alloantigen H-2.2 was tested. High and low antibody-producing strains were distinguished by their anti-H-2.2 hemagglutinating respones. However, these strains do not differ in their ability to respond to these antigenic differences in the mixed lymphocyte culture. The humoral response to the H-2.2 alloantigen was shown to be controlled by two interacting genes localized within the H-2 complex. Thus, F1 hybrids prepared between parental low responder strains could yield high level immune responses. In addition, strains bearing recombinant H-2 haplotypes were used to map the two distinct genes controlling the immune response. The alleles at each locus were shown to be highly polymorphic as evidenced by the asymmetric complementation patterns observed. The restricted interactions of specific alleles was termed coupled complementation. The significance of the results in the terms of mechanisms of Ir gene control are discussed.

scholarly journals Stromal hyaluronan accumulation is associated with low immune response and poor prognosis in pancreatic cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyösti Tahkola ◽  
Maarit Ahtiainen ◽  
Jukka-Pekka Mecklin ◽  
Ilmo Kellokumpu ◽  
Johanna Laukkarinen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cell ◽  
Geographical Area ◽  
Prognostic Significance ◽  
Staining Intensity ◽  
Ductal Adenocarcinoma ◽  
Poor Survival ◽  
Negative Prognostic Factor ◽  
High Level ◽  
Immune Cell Score

AbstractHyaluronan (HA) accumulation has been associated with poor survival in various cancers, but the mechanisms for this phenomenon are still unclear. The aim of this study was to investigate the prognostic significance of stromal HA accumulation and its association with host immune response in pancreatic ductal adenocarcinoma (PDAC). The study material consisted of 101 radically treated patients for PDAC from a single geographical area. HA staining was evaluated using a HA-specific probe, and the patterns of CD3, CD8, CD73 and PD-L1 expression were evaluated using immunohistochemistry. HA staining intensity of tumour stromal areas was assessed digitally using QuPath. CD3- and CD8-based immune cell score (ICS) was determined. High-level stromal HA expression was significantly associated with poor disease-specific survival (p = 0.037) and overall survival (p = 0.013) In multivariate analysis, high-level stromal HA expression was an independent negative prognostic factor together with histopathological grade, TNM stage, CD73 positivity in tumour cells and low ICS. Moreover, high-level stromal HA expression was associated with low ICS (p = 0.017). In conclusion, stromal HA accumulation is associated with poor survival and low immune response in PDAC.

scholarly journals Allogeneic chimerism with low-dose irradiation, antigen presensitization, and costimulator blockade in H-2 mismatched mice

Blood ◽  
2001 ◽  
Vol 97 (2) ◽  
pp. 557-564 ◽  
Author(s):  
Peter J. Quesenberry ◽  
Suju Zhong ◽  
Han Wang ◽  
Marc Stewart
Keyword(s):  
Low Dose ◽  
Great Majority ◽  
Cd40 Ligand ◽  
Third Party ◽  
Whole Body ◽  
Spleen Cells ◽  
Graft Versus Host ◽  
Dose Irradiation ◽  
Unique Model ◽  
High Level

Abstract We have previously shown that the keys to high-level nontoxic chimerism in syngeneic models are stem cell toxic, nonmyelotoxic host treatment as provided by 100-cGy whole-body irradiation and relatively high levels of marrow stem cells. This approach was unsuccessful in H-2 mismatched B6.SJL to BALB/c marrow transplants, but with tolerization, stable multilineage chimerism was obtained. Ten million B6.SJL spleen cells were infused intravenously into BALB/c hosts on day −10 and (MR-1) anti-CD40 ligand monoclonal antibody (mAb) injected intraperitoneally at varying levels on days −10, −7, −3, 0, and +3 and the BALB/c mice irradiated (100 cGy) and infused with 40 million B6.SJL/H-2 mismatched marrow cells on day 0. Stable multilineage chimerism at levels between 30% to 40% was achieved in the great majority of mice at 1.6 mg anti-CD40 ligand mAb per injection out to 64 weeks after transplantation, without graft-versus-host disease. The transplanted mice were also tolerant of donor B6.SJL, but not third-party CBA/J skin grafts at 8 to 9 and 39 to 43 weeks after marrow transplantation. These data provide a unique model for obtaining stable partial chimerism in H-2 mismatched mice, which can be applied to various clinical diseases of man such as sickle cell anemia, thalassemia, and autoimmune disorders.

High level expression of the Drosophila Toll receptor ectodomain and crystallization of its complex with the morphogen Spätzle

2013 ◽  
Vol 394 (8) ◽  
pp. 1091-1096 ◽  
Author(s):  
Marco Stelter ◽  
Uwe Fandrich ◽  
Kati Franzke ◽  
Angelika Schierhorn ◽  
Constanze Breithaupt ◽  
...  
Keyword(s):  
Immune Response ◽  
High Level Expression ◽  
Receptor Ligand ◽  
High Affinity ◽  
Cystine Knot ◽  
Toll Receptor ◽  
Cystine Knot Protein ◽  
High Yields ◽  
High Level ◽  
Affinity Interaction

Abstract Drosophila Toll receptors are involved in embryonic development and in the immune response of adult flies. In both processes, the Toll receptor ligand is the NGF-like cystine knot protein Spätzle. Here we present the expression of Toll receptor ectodomain in Schneider cells at high yields and demonstrate a high affinity interaction with the refolded and trypsin-processed Spätzle cystine knot domain dimer. Poorly and anisotropically diffracting crystals of the complex could be improved by deglycosylation and dehydration, paving the way for structural analyses of the Toll-Spätzle interaction.

scholarly journals Heavy metal intoxication compromises the host cytokine response in Ascaris Suum model infection

2016 ◽  
Vol 53 (1) ◽  
pp. 14-23 ◽  
Author(s):  
E. Dvorožňáková ◽  
M. Dvorožňáková ◽  
J. Šoltys
Keyword(s):  
Heavy Metal ◽  
Immune Response ◽  
Ascaris Suum ◽  
Cytokine Response ◽  
Parasitic Infections ◽  
Tnf Α ◽  
Ifn Γ ◽  
High Level ◽  
Larval Burden ◽  
Heavy Metal Intoxication

SummaryLead (Pb), Cadmium (Cd) and Mercury (Hg) are recognized for their deleterious effect on the environment and immunity where subsequently compromised immune response affects the susceptibility to the potential parasitic infections. This study examined the host cytokine response after heavy metal intoxication (Pb, Cd, and Hg) and subsequent Ascaris suum infection in BALB/c mice. Pb modulated murine immune response towards the Th2 type of response (delineated by IL-5 and IL-10 cytokine production) what was also dominant for the outcome of A. suum infection. Chronic intoxication with Pb caused a more intensive development of the parasite infection. Cd stimulated the Th1 immune response what was associated with increase in IFN-γ production and reduction of larvae present in the liver of intoxicated mice. The larval burden was also low in mice intoxicated with Hg. This was probably not related to the biased Th1/Th2 type of immune response, but rather to the bad host conditions caused by mercury toxicity and high level of pro-cachectic cytokine TNF-α.

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