scholarly journals A detailed analysis of innate and adaptive immune responsiveness upon infection with Salmonella enterica serotype Enteritidis in young broiler chickens

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Nathalie Meijerink ◽  
Robin H. G. A. van den Biggelaar ◽  
Daphne A. van Haarlem ◽  
J. Arjan Stegeman ◽  
Victor P. M. G. Rutten ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Nk Cells ◽  
Salmonella Enterica ◽  
Broiler Chickens ◽  
Immune Modulation ◽  
Adaptive Immune Responses ◽  
Activation Markers ◽  
Adaptive Immune ◽  
Adaptive Immune Cells

AbstractSalmonella enterica serotype Enteritidis (SE) is a zoonotic pathogen which causes foodborne diseases in humans as well as severe disease symptoms in young chickens. More insight in innate and adaptive immune responses of chickens to SE infection is needed to understand elimination of SE. Seven-day-old broiler chickens were experimentally challenged with SE and numbers and responsiveness of innate and adaptive immune cells as well as antibody titers were assessed. SE was observed in the ileum and spleen of SE-infected chickens at 7 days post-infection (dpi). At 1 dpi numbers of intraepithelial cytotoxic CD8+ T cells were significantly increased alongside numerically increased intraepithelial IL-2Rα+ and 20E5+ natural killer (NK) cells at 1 and 3 dpi. At both time points, activation of intraepithelial and splenic NK cells was significantly enhanced. At 7 dpi in the spleen, presence of macrophages and expression of activation markers on dendritic cells were significantly increased. At 21 dpi, SE-induced proliferation of splenic CD4+ and CD8+ T cells was observed and SE-specific antibodies were detected in sera of all SE-infected chickens. In conclusion, SE results in enhanced numbers and activation of innate cells and we hypothesized that in concert with subsequent specific T cell and antibody responses, reduction of SE is achieved. A better understanding of innate and adaptive immune responses important in the elimination of SE will aid in developing immune-modulation strategies, which may increase resistance to SE in young broiler chickens.

scholarly journals Contribution of innate and adaptive immune cells to the elimination of Salmonella enterica serotype Enteritidis infection in young broiler chickens

2021 ◽  
Author(s):  
Nathalie Meijerink ◽  
Robin H.G.A. van den Biggelaar ◽  
Daphne A. van Haarlem ◽  
J. Arjan Stegeman ◽  
Victor P.M.G. Rutten ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Nk Cells ◽  
Salmonella Enterica ◽  
Broiler Chickens ◽  
Immune Modulation ◽  
Severe Disease ◽  
Antibody Responses ◽  
Adaptive Immune

AbstractSalmonella enterica serotype Enteritidis (SE) is a zoonotic pathogen which causes foodborne diseases in humans through contaminated poultry products, as well as severe disease symptoms in young chickens. More insight in innate and adaptive immune responses of chickens to SE infection is needed to understand elimination of SE. Seven-day-old broiler chickens were experimentally challenged with SE and numbers and responsiveness of innate immune cells including natural killer (NK) cells, macrophages and dendritic cells (DCs) were assessed during 21 days post-infection (dpi). In parallel, numbers and function of γδ T cells, CD8+ and CD4+ T cells as well as antibody titres were determined. SE was observed in the intestine and spleen of SE-infected chickens at 7 dpi. NK and T cells responded first to SE at 1 and 3 dpi as indicated by increased numbers of intestinal IL-2Rα+ and 20E5+ NK cells, in addition to enhanced activation of intestinal and splenic NK cells. At 7 dpi in the spleen, the presence of macrophages and the expression of activation markers on DCs was increased. At 21 dpi, an increase in intestinal γδ and CD8+ T cell numbers was observed. Furthermore, SE-specific proliferation of splenic CD4+ and CD8+ T cells was observed and SE-specific antibodies were detected in all blood samples of SE-infected chickens. In conclusion, SE results in enhanced numbers and activation of innate cells during early stages of infection and it is hypothesized that in concert with subsequent specific T cell and antibody responses, reduction of SE in infected chickens is achieved. A better understanding of innate and adaptive immune responses important in the elimination of SE will aid in developing immune-modulation strategies, which may increase resistance and prevent SE infection and colonization in young broiler chickens and hence increase food safety for humans.Author summarySalmonella enterica serotype Enteritidis (SE) causes foodborne zoonotic diseases in humans, as well as a severe disease in young chickens. As a consequence of which health and welfare of humans and chickens are affected, resulting in substantial economic losses. To enable development of immune-mediated prevention strategies in chickens, more insight in the immune responses to SE is needed to understand how the infection is eliminated. For this purpose, we investigated non-specific and specific immune responses upon experimental SE infection in young broiler chickens. In this study, we found SE in the intestine and spleen of SE-infected chickens at 7 days post-infection (dpi). We show that natural killer (NK) cells respond first by enhanced presence and activation, followed by increased presence of macrophages and activation of dendritic cells. These early responses are hypothesized to stimulate the observed subsequent specific T cell and antibody responses. Better understanding of immune responses important in the elimination of SE will aid in developing immune-modulation strategies, which may increase resistance and prevent SE infection and colonization in young chickens and hence reduce SE-related foodborne illness in humans.

scholarly journals The PD-L1 and TLR7 dual-targeting nanobody-drug conjugate exerts potent antitumor efficacy by orchestrating innate and adaptive immune responses

2021 ◽  
Author(s):  
Xiaolu Yu ◽  
Yiru Long ◽  
Binfan Chen ◽  
Yongliang Tong ◽  
Xiaomin Jia ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Antitumor Efficacy ◽  
Antitumor Effects ◽  
Adaptive Immune Responses ◽  
Drug Conjugate ◽  
Adaptive Immune ◽  
Dual Targeting ◽  
Adaptive Immune Cells ◽  
Tumor Tissues

A variety of tumors are insensitive to immune checkpoint blockade (ICB) therapy. We propose that ICB therapy alone is insufficient to fully reactivate antitumor T cells, while effective mobilization of antigen-presenting cells (APCs) to assist adaptive immune cell activation can lead to potent antitumor effects with broad responsiveness. The Toll-like receptor 7 (TLR7) agonist SZU-101 we developed can induce the innate immune response against tumors and increase the immunogenicity of tumors. Interestingly, SZU-101-induced upregulation of programmed death ligand 1 (PD-L1) expression in tumor tissues can further enhance the response rate of the PD-L1 antibody. In addition, PD-L1 nanobodies have better solid tumor penetration ability, and because of this ability, they can be used to precisely deliver SZU-101 to tumor tissues. Therefore, a PD-L1 and TLR7 dual-targeting nanobody-drug conjugate (NDC), a novel drug molecule, was developed. We found that TLR7 agonists and PD-L1 nanobodies act synergistically and that NDC treatment reshapes the tumor immune microenvironment, activates both innate and adaptive immune cells, and exerts antitumor effects in both hot and cold tumors primarily through CD8+ T cells and natural killer (NK) cells. Our data show that a PD-L1 and TLR7 dual-targeting NDC can exhibit potent antitumor efficacy by orchestrating innate and adaptive immune responses and shows good prospects for clinical development.

scholarly journals Mast cells and γδ T cells are largely dispensable for adaptive immune responses after laser-mediated epicutaneous immunization

Vaccine ◽  
2020 ◽  
Vol 38 (5) ◽  
pp. 1015-1024
Author(s):  
Isabella A. Joubert ◽  
Daniel Kovacs ◽  
Sandra Scheiblhofer ◽  
Petra Winter ◽  
Evgeniia Korotchenko ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cells ◽  
Immune Responses ◽  
Γδ T Cells ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

scholarly journals P01.10 IFNy secretion of adaptive and innate immune cells as a parameter to display leukaemia derived dendritic cell (DCleu) mediated immune responses in AML

2020 ◽  
Vol 8 (Suppl 2) ◽  
pp. A13.1-A13
Author(s):  
LK Klauer ◽  
O Schutti ◽  
S Ugur ◽  
F Doraneh-Gard ◽  
N Rogers ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Immune Cells ◽  
Gm Csf ◽  
Adaptive Immune ◽  
Cik Cells ◽  
Adaptive Immune Cells ◽  
Suitable Parameter

BackgroundMyeloid leukaemic blasts can be converted into leukaemia derived dendritic cells (DCleu) with blastmodulatory Kit-I and Kit-M, which have the competence to regularly activate T and immunoreactive cells to gain anti-leukaemic activity or rather cytotoxicity. As innate and adaptive immune responses are notably promoted by the cytokine interferon gamma (IFNy), we hypothesised that the IFNy secretion could be a suitable parameter to display DC/DCleu mediated immunologic activity and even anti-leukaemic cytotoxicity.Materials and MethodsDC/DCleu were generated from leukaemic WB with Kit-I (GM-CSF + OK-432) and Kit-M (GM-CSF + PGE1) and used to stimulate T cell enriched immunoreactive cells. Initiated anti-leukaemic cytotoxicity was investigated with a cytotoxicity fluorolysis assay (CTX). Initiated IFNy secretion of innate and adaptive immune cells (T cells, TCD4+ cells, TCD8+ cells, NKCD56+ cells, NKCD161+ cells, CIKCD56+ cells, CIKCD161+ cells and iNKT) was investigated with a cytokine secretion assay (CSA). In some cases IFNy production was additionally evaluated with an intracellular cytokine assay (ICA). Conclusively, the IFNy secretion of immunoreactive cells was correlated with the anti-leukaemic cytotoxicity.ResultsSignificant amounts of DC and DCleu as well as migratory DC and DCleu could be generated with Kit-I and Kit-M without induction of blast proliferation. T cell enriched immunoreactive cells stimulated with DC/DCleu showed an increased anti-leukaemic cytotoxicity and an increased IFNy secretion of T, NK and CIK cells compared to control. Both the CSA and ICA yielded comparable amounts of IFNy positive innate and adaptive immune cells. The correlation between the IFNy secretion of immunoreactive cells and the anti-leukaemic cytotoxicity showed a positive relationship in T cells, TCD4+ cells, TCD8+ cells and NKCD56+ cells.ConclusionsWe found blastmodulatory Kit-I and Kit-M competent to generate DC/DCleu from leukaemic WB. Stimulation of T cell enriched immunoreactive cells with DC/DCleu regularly resulted in an increased anti-leukaemic cytotoxicity and an increased IFNy dependent immunological activity of T, NK and CIK cells compared to control. Moreover the anti-leukaemic cytotoxicity positively correlated with the IFNy secretion in T cells, TCD4+ cells, TCD8+ cells, NKCD56+ cells. We therefore consider the IFNy secretion of innate and adaptive immune cells to be a suitable parameter to assess the efficacy of in vitro and potentially in vivo AML immunotherapy. The CSA in this regard proved to be a convenient and reproducible technique to detect and phenotypically characterise IFNy secreting cells of the innate and adaptive immune system.Disclosure InformationL.K. Klauer: None. O. Schutti: None. S. Ugur: None. F. Doraneh-Gard: None. N. Rogers: None. M. Weinmann: None. D. Krämer: None. A. Rank: None. C. Schmid: None. B. Eiz-Vesper: None. H.M. Schmetzer: None.

CD154:CD40 Co-Stimulatory Blockade: A Novel Approach To Prevent Sensitization to Donor Alloantigens.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1273-1273
Author(s):  
Hong Xu ◽  
Jun Yan ◽  
Suzanne T. Ildstad
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
B Cell ◽  
Germinal Center ◽  
Cell Activation ◽  
Cell Tolerance ◽  
B Cell Activation ◽  
B Cell Tolerance ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

Abstract Introduction: Recipient sensitization is one of the most critical problems facing clinical transplantation. Allosensitized recipients often rapidly reject vascularized solid organ grafts as a result of preformed anti-donor antibody. Similarly, bone marrow transplantation for sickle cell disease and thalassemia is limited by sensitization from transfusion. A method to prevent sensitization would have a significant impact on transplant outcomes. Until recently, T cells were believed to be the primary effector cell in the induction of adaptive immune responses. We recently found that humoral immunity provides a dominant barrier in allosensitization to MHC antigens. B cell activation occurs through T-cell-dependent responses via signaling from the co-stimulatory molecule CD154 (on T cells) to its ligand CD40 (on B cells). Here, we examined whether blocking the costimulatory interaction between T and B cells during exposure to alloantigen would prevent allosensitization. Materials and Methods: Mice deficient for CD154 molecule (CD154−/ −, H-2b), α β-TCR+ T cells (TCRβ −/ −, H-2b); or wild type B6 (H-2b) mice received allogeneic BALB/c (H-2d) skin grafts (SG) on day 0. Some B6 mice were also treated with anti-CD154 (day0 and day+3) and/or anti-α β-TCR mAb (day-3) peritransplant. Antibodies were detected by flow cytometry cross-match (FCM) assay and reported as mean fluorescence intensity (MFI). Results: CD154−/ − mice rejected primary BALB/c SG with a time course similar to normal B6 controls (12.4 ± 2.1 vs. 12.7 ± 2.4 days). TCRβ −/ − mice accepted SG permanently (>120 days). Notably, anti-donor antibody was not generated in either the CD154−/ − or TCRβ −/ − mice (MFI: 4.1 ± 0.1 and 4.2 ± 0.4) after SG compared with Ab in naïve serum (3.0±0.2). Sensitized B6 mice had significantly higher antibody titers (106.8 ± 35.1) 4 weeks after SG rejection. A second SG transplanted 5 to 7 weeks after the first graft was rejected at an accelerated rate (9.0 ± 0.8 days, P < 0.05) in the CD154−/ − mice, but no anti-donor MHC antibody was produced. Second grafts placed on TCRβ −/ − mice were accepted, as were the primary SG. In normal B6 recipients pretreated with anti-CD154 or anti-α β-TCR alone, SG survival was not significantly prolonged. The Ab titers were only slightly higher in mice treated with anti-CD154 (5.9±3.4; P>0.05) than in naïve mice, and significantly higher in mice treated with mAb anti-α β-TCR (45.1±25.6; P=0.03). The combined treatment with both mAbs resulted in complete abrogation of Ab production (4.2±0.9) and 70% of skin grafts survived >100 days. Germinal center formation, reflective of B cell activation, was completely disrupted in mice treated with anti-CD154 alone or combined with anti-α β-TCR. Conclusion: These results suggest that the CD40/CD154 co-stimulatory pathway is critically important in B cell activation to generate alloantibody. Notably, blocking molecular interactions between CD40/CD154 abrogated the generation of antibody and blocked germinal center formation, inducing B cell tolerance. The additional removal of recipient T cells in the context of co-stimulatory blockade resulted in the induction of T as well as B cell tolerance. These findings are the first demonstration that sensitization can be prevented through blockade of co-stimulatory interactions in the generation of adaptive immune responses and could have a significant impact on management of sensitized recipients in the clinic.

Engaging the NKG2D Receptor with a Novel Bispecific Protein (ULBP2-antiCD138) Activates NK Cells and Has Potent Antitumor Activity Against Human Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5157-5157
Author(s):  
Elke Pogge von Strandmann ◽  
Michael Hallek ◽  
Andreas Engert
Keyword(s):  
Multiple Myeloma ◽  
Immune Responses ◽  
Nk Cells ◽  
Clinical Investigation ◽  
Human Peripheral Blood ◽  
Malignant Cells ◽  
Adaptive Immune Responses ◽  
Nude Mouse Model ◽  
Ifn Gamma ◽  
Adaptive Immune

Abstract NK cells, a component of the innate immune system, attack virus-infected and malignant cells without prior antigen stimulation, mediate cellular cytotoxicity and produce cytokines such as interferon gamma (IFN-gamma) upon stimulation. There is growing evidence that NK cells also participate directly in adaptive immune responses, mainly by cross-talk with dendritic cells. One key factor responsible for the activation of innate and adaptive immune responses is NKG2D, a stimulatory receptor expressed on natural killer cells that binds to cellular ligands on malignant cells. Therefore we designed a recombinant NK receptor ligand (ULBP2) fused to an antibody (BB4) detecting the tumor antigen CD138 which is overexpressed on a variety of malignancies including multiple myeloma (MM). The major findings were that (1) ULBP2-BB4 bound both NK cells and tumor cells, (2) triggered NK-mediated cell lysis of CD138+ malignant cell lines and primary MM cells in the allogenic and autologous setting, (3) activated IFN-gamma secretion of NK cells exposed to immobilized protein, and (4) the co-therapy with ULBP-BB4 and human peripheral blood lymphocytes abrogated the tumor growth in a nude mouse model with subcutaneously growing MM cells. This is the first report on the design, expression, purification and functional pre-clinical investigation of a recombinant NKG2D ligand. The results suggest not only a potential clinical use of this novel construct in patients with MM, but might also offer an innovative therapy approach which is based on NKG2D engagement transferable to other malignancies.

scholarly journals Early IL-17 Production by Intrahepatic T Cells Is Important for Adaptive Immune Responses in Viral Hepatitis

2012 ◽  
Vol 190 (2) ◽  
pp. 621-629 ◽  
Author(s):  
Lifei Hou ◽  
Zuliang Jie ◽  
Mayura Desai ◽  
Yuejin Liang ◽  
Lynn Soong ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Viral Hepatitis ◽  
Adaptive Immune Responses ◽  
Adaptive Immune
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