scholarly journals Tolerogenic Immunoregulation towards Salmonella Enteritidis Contribute to Colonization Persistence in Young Chicks

2021 ◽  
Author(s):  
Khin K.Z. Mon ◽  
Colin Kern ◽  
Ganrea Chanthavixay ◽  
Ying Wang ◽  
Huaijun Zhou
Keyword(s):  
T Cells ◽  
Salmonella Enteritidis ◽  
Immunological Response ◽  
Negative Regulator ◽  
Infection Model ◽  
Lag Phase ◽  
Term Survival ◽  
Immunological Responses ◽  
Cecal Tonsil ◽  
Potential Pathogen

Long-term survival and the persistence of the bacteria in the host suggest either host unresponsiveness or induction of immunological tolerant response towards the pathogen. The role of host immunological response to persistent colonization of Salmonella Enteritidis (SE) in chicken remains poorly understood. In the current study, we performed a cecal tonsil transcriptome analysis in a two-week-old SE persistent infection model to comprehensively examine the dynamic of host immunological responses in the chicken gastrointestinal tract. Our results revealed an overall host tolerogenic adaptive immune regulation occurrence in one of the major gut-associated lymphoid tissue, cecal tonsil, during SE infection. Specifically, we observed consistent down-regulation of metallothionein 4 at all four post-infection time points (3,7,14 & 21dpi) which suggested potential pathogen-associated manipulation of the host zinc regulation as well as possible immune modulatory effect. Furthermore, delayed activation in the B cells receptor signaling pathway and failure to sustain its active state during the lag phase of infection was further supported by an insignificant production of both intestinal and circulatory antibody levels. Tag of war for IL-2 regulation between effector T cells and regulatory T cells appear to have the consequential outcome on up-regulation in Transducer of ERBB2 also known as TOB pathway, a negative regulator of T cell proliferation. In conclusion, current work highlighted the overall host tolerogenic immune response that promoted persistent colonization of SE in young layer chicks.

The kinetics of immunological responses to microfilariae in a murine host: experimental and mathematical studies

Parasitology ◽  
1997 ◽  
Vol 114 (3) ◽  
pp. 237-243 ◽  
Author(s):  
C. J. RHODES ◽  
S. G. FOLKARD ◽  
A. E. BIANCO ◽  
R. M. ANDERSON
Keyword(s):  
Mathematical Model ◽  
T Cells ◽  
Good Description ◽  
Secondary Infection ◽  
Parasitic Infection ◽  
Immunological Response ◽  
Experimental Results ◽  
Immunological Responses ◽  
Infection Dynamics ◽  
Time Post Infection

We present a mathematical model which is used to interpret the dynamics of the immunological response of a mouse host to infection with the filarial worm Onchocerca lienalis. The model mimics changes in worm burden over time post-infection and after reinfection and its behaviour provides a good description of experimental results. Measured production of T-cells and eosinophils is also compared with the predictions of the model. Our results show that the immune response mechanism proposed on the basis of experimental results, involving CD4+ T-cells and eosinophil destruction of the parasite, is supported by the insights gained from the mathematical model. Also, using the parameters estimated to describe the primary infection dynamics, the degree of acquired immunity to secondary infection is also well described by the model. Our analysis highlights the importance of obtaining quantitative measures of the many rate parameters involved in even the simplest interpretations of immunological responses to parasitic infection.

scholarly journals 678 Addition of a single bacteria facilitates anti-tumor immunity and long-term survival in colorectal cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A717-A717
Author(s):  
Abigail Overacre-Delgoffe ◽  
Anthony Cillo ◽  
Hannah Bumgarner ◽  
Ansen Burr ◽  
Justin Tometich ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Tumor Immunity ◽  
Tumor Burden ◽  
Intestinal Microbiome ◽  
Tumor Control ◽  
Mesenteric Lymph Nodes ◽  
Term Survival ◽  
16S Sequencing ◽  
Tumor Bearing

BackgroundColorectal cancer remains one of the most common and deadliest cancers worldwide and effective therapies are lacking. While immunotherapy has revolutionized treatment for many cancers, the overwhelming majority of colorectal cancer patients are non-responsive and the 5-year survival rate for advanced disease is <20%. Immunotherapeutic response has been associated with select members of the microbiome in melanoma; however, the potential benefit in colorectal cancer and the underlying mechanisms remain unclear. We sought to determine how specific members of the intestinal microbiome affect anti-tumor immunity in colorectal cancer (CRC) in hopes of discovering novel treatments and revealing potential hurdles to current therapeutic response in CRC patients.MethodsWe utilized a carcinogen-induced mouse model of CRC and colonized half of the tumor-bearing mice with Helicobacter hepaticus (Hhep) 7 weeks post AOM. Tumor number was assessed 12 weeks post AOM. We isolated lymphocytes from the lamina propria, colonic epithelium, mesenteric lymph nodes, and tumor(s) to track the spatial and transcriptional Hhep-specific and endogenous immune responses during tumor progression through 5’ single cell RNAseq, flow cytometry, and immunofluorescence. In addition, we utilized 16S sequencing and FISH to track Hhep colonization, location within the colon, and its impact on the surrounding microbiome.ResultsWe have found that rational modification of the microbiome of colon tumor-bearing mice through addition of a single bacteria, Hhep, led to tumor control or clearance and a significant survival advantage. Colonization led to the expansion of the lymphatic network and development of numerous peri- or intra-tumoral tertiary lymphoid structures (TLS) composed of Hhep-specific CD4 T follicular helper cells (TFH) as well as the bacteria itself. This led to an overall ‘heating’ of the tumor, wherein we saw an increase of CD4 T cell infiltration to the tumor core as well as an increase in CD103+ type 1 DC (cDC1) recruitment through increased chemokines such as CCL5 and XCL1. Hhep-specific TFH were both necessary and sufficient to drive TLS formation, increased immune invasion, and anti-tumor immunity.ConclusionsWe have shown that addition of a single bacteria, Hhep, leads to a reduction in CRC tumor burden or clearance through lymphatic expansion, TLS formation, and remodeling of the tumor microenvironment, and that Hhep-specific T cells are required for tumor control. These studies suggest that rational modification of the microbiome and microbiome-specific T cells can positively impact anti-tumor immunity and may represent a unique immunotherapeutic target to turn resistant tumors into responsive tumors.

scholarly journals Alpha-Fetoprotein- and CD40Ligand-Expressing Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3375
Author(s):  
Annabelle Vogt ◽  
Farsaneh Sadeghlar ◽  
Tiyasha H. Ayub ◽  
Carlo Schneider ◽  
Christian Möhring ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Dendritic Cells ◽  
Tumor Regression ◽  
Combined Therapy ◽  
Term Survival ◽  
Effector Cells ◽  
Tumor Environment ◽  
The Impact

Dendritic cells (DC) as professional antigen presenting cells are able to prime T-cells against the tumor-associated antigen α-fetoprotein (AFP) for immunotherapy of hepatocellular carcinoma (HCC). However, a strong immunosuppressive tumor environment limits their efficacy in patients. The co-stimulation with CD40Ligand (CD40L) is critical in the maturation of DC and T-cell priming. In this study, the impact of intratumoral (i.t.) CD40L-expressing DC to improve vaccination with murine (m)AFP-transduced DC (Ad-mAFP-DC) was analyzed in subcutaneous (s.c.) and orthotopic murine HCC. Murine DC were adenovirally transduced with Ad-mAFP or Ad-CD40L. Hepa129-mAFP-cells were injected into the right flank or the liver of C3H-mice to induce subcutaneous (s.c.) and orthotopic HCC. For treatments, 106 Ad-mAFP-transduced DC were inoculated s.c. followed by 106 CD40L-expressing DC injected intratumorally (i.t.). S.c. inoculation with Ad-mAFP-transduced DC, as vaccine, induced a delay of tumor-growth of AFP-positive HCC compared to controls. When s.c.-inoculation of Ad-mAFP-DC was combined with i.t.-application of Ad-CD40L-DC synergistic antitumoral effects were observed and complete remissions and long-term survival in 62% of tumor-bearing animals were achieved. Analysis of the tumor environment at different time points revealed that s.c.-vaccination with Ad-mAFP-DC seems to stimulate tumor-specific effector cells, allowing an earlier recruitment of effector T-cells and a Th1 shift within the tumors. After i.t. co-stimulation with Ad-CD40L-DC, production of Th1-cytokines was strongly increased and accompanied by a robust tumor infiltration of mature DC, activated CD4+-, CD8+-T-cells as well as reduction of regulatory T-cells. Moreover, Ad-CD40L-DC induced tumor cell apoptosis. Intratumoral co-stimulation with CD40L-expressing DC significantly improves vaccination with Ad-mAFP-DC in pre-established HCC in vivo. Combined therapy caused an early and strong Th1-shift in the tumor environment as well as higher tumor apoptosis, leading to synergistic tumor regression of HCC. Thus, CD40L co-stimulation represents a promising tool for improving DC-based immunotherapy of HCC.

HOXB9 acts as a negative regulator of activated human T cells in response to amino acid deficiency

2016 ◽  
Vol 94 (6) ◽  
pp. 612-617 ◽  
Author(s):  
Keitaro Hayashi ◽  
Motoshi Ouchi ◽  
Hitoshi Endou ◽  
Naohiko Anzai
Keyword(s):  
T Cells ◽  
Amino Acid ◽  
Negative Regulator ◽  
Amino Acid Deficiency ◽  
Human T Cells ◽  
Acid Deficiency

scholarly journals CD27 Expression Promotes Long-Term Survival of Functional Effector–Memory CD8+Cytotoxic T Lymphocytes in HIV-infected Patients

2004 ◽  
Vol 200 (11) ◽  
pp. 1407-1417 ◽  
Author(s):  
Adrian F. Ochsenbein ◽  
Stanley R. Riddell ◽  
Michele Brown ◽  
Lawrence Corey ◽  
Gabriela M. Baerlocher ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Cd8 T Cells ◽  
Interleukin 2 ◽  
Tumor Necrosis Factor Receptor ◽  
Cell Receptor ◽  
Effector Memory ◽  
Term Survival ◽  
Functional Consequences

Human immunodeficiency virus (HIV)-specific CD8+ T cells persist in high frequencies in HIV-infected patients despite impaired CD4+ T helper response to the virus, but, unlike other differentiated effector cytotoxic T lymphocytes, most continue to express the tumor necrosis factor receptor family member CD27. Because the ligand for CD27 (CD70) is also overexpressed in HIV-infected hosts, we examined the nature of expression and potential functional consequences of CD27 expression on HIV-specific CD8+ T cells. Analysis of CD27+ and CD27− T cells derived from the same HIV-specific clone revealed that retention of CD27 did not interfere with acquisition of effector functions, and that after T cell receptor stimulation, CD27+ cells that concurrently were triggered via CD27 exhibited more resistance to apoptosis, interleukin 2 production, and proliferation than CD27− T cells. After transfer back into an HIV-infected patient, autologous HIV-specific CD27− T cells rapidly disappeared, but CD27+ T cells derived from the same clone persisted at high frequency. Our findings suggest that the CD27–CD70 interaction in HIV infection may provide CD27+ CD8+ T cells with a survival advantage and compensate for limiting or absent CD4+ T help to maintain the CD8 response.

scholarly journals Study of the effect exerted by fructo-oligosaccharides from yacon (Smallanthus sonchifolius) root flour in an intestinal infection model with Salmonella Typhimurium

2012 ◽  
Vol 109 (11) ◽  
pp. 1971-1979 ◽  
Author(s):  
Eva Velez ◽  
Natalia Castillo ◽  
Oscar Mesón ◽  
Alfredo Grau ◽  
María E. Bibas Bonet ◽  
...  
Keyword(s):  
Mouse Model ◽  
Protective Effect ◽  
Salmonella Enteritidis ◽  
Inflammatory Responses ◽  
Intestinal Barrier ◽  
Secretory Iga ◽  
Infection Model ◽  
Enteric Infection ◽  
Smallanthus Sonchifolius ◽  
Iga Production

Beneficial effects of prebiotics like inulin and fructo-oligosaccharides (FOS) have been proven in health and nutrition. Yacon (Smallanthus sonchifolius), an Andean crop, contains FOS (50–70 % of its dry weight) and, therefore, is considered a prebiotic. Commercial FOS can up-regulate total secretory IgA (S-IgA) in infant mice, prevent infection with Salmonella in swine or enhance immune response for Salmonella vaccine in a mouse model. Previously, we found that administration of yacon root flour regulates gut microbiota balance and has immunomodulatory effects without inflammatory responses. The aim of the present paper is to analyse if yacon prevents enteric infection caused by a strain of Salmonella enteritidis serovar Typhimurium (S. Typhimurium) in a mouse model. BALB/c mice were supplemented with yacon flour (45 d), challenged with S. Typhimurium and killed to study pathogen translocation, total and specific IgA production by ELISA, presence of IgA and other cytokines and Toll-like receptor 4 (TLR4) and clustor of differentiation 206 (CD206) receptors positive cells by immunofluorescence and histological changes. Yacon flour administration had a protective effect from 15 to 30 d of treatment. We found a peak of total S-IgA production without translocation of the pathogen for these periods. At 30 d, there was an increase in IL-6 and macrophage inflammatory proteins-1α+ cells and expression of the receptors CD206 and TLR4. Yacon flour did not have incidence in pathogen-specific S-IgA production. Longer periods (45 d) of administration had no protective effect. Therefore, yacon can prevent enteric infection caused by S. Typhimurium when given up to 30 d; this effect would be mediated by enhancing non-specific immunity, such as total S-IgA, that improves the immunological intestinal barrier.

scholarly journals Prospective observational study of SARS-CoV-2 infection, transmission and immunity in a cohort of households in Liverpool City Region, UK (COVID-LIV): a study protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. e048317
Author(s):  
Wega Setiabudi ◽  
Daniel Hungerford ◽  
Krishanthi Subramaniam ◽  
Natasha Marcella Vaselli ◽  
Victoria E Shaw ◽  
...  
Keyword(s):  
Observational Study ◽  
Prospective Observational Study ◽  
Initial Period ◽  
Immunological Response ◽  
Nucleic Acid Amplification ◽  
Service Research ◽  
City Region ◽  
Immunological Responses ◽  
Household Transmission ◽  
Population Spread

IntroductionThe emergence and rapid spread of COVID-19 have caused widespread and catastrophic public health and economic impact, requiring governments to restrict societal activity to reduce the spread of the disease. The role of household transmission in the population spread of SARS-CoV-2, and of host immunity in limiting transmission, is poorly understood. This paper describes a protocol for a prospective observational study of a cohort of households in Liverpool City Region, UK, which addresses the transmission of SARS-CoV-2 between household members and how immunological response to the infection changes over time.Methods and analysisHouseholds in the Liverpool City Region, in which members have not previously tested positive for SARS-CoV-2 with a nucleic acid amplification test, are followed up for an initial period of 12 weeks. Participants are asked to provide weekly self-throat and nasal swabs and record their activity and presence of symptoms. Incidence of infection and household secondary attack rates of COVID-19 are measured. Transmission of SARS-CoV-2 will be investigated against a range of demographic and behavioural variables. Blood and faecal samples are collected at several time points to evaluate immune responses to SARS-CoV-2 infection and prevalence and risk factors for faecal shedding of SARS-CoV-2, respectively.Ethics and disseminationThe study has received approval from the National Health Service Research Ethics Committee; REC Reference: 20/HRA/2297, IRAS Number: 283 464. Results will be disseminated through scientific conferences and peer-reviewed open access publications. A report of the findings will also be shared with participants. The study will quantify the scale and determinants of household transmission of SARS-CoV-2. Additionally, immunological responses before and during the different stages of infection will be analysed, adding to the understanding of the range of immunological response by infection severity.

Diversity, localization and (patho)physiology of mature lymphocyte populations in the bone marrow

Blood ◽  
2021 ◽  
Author(s):  
Christian M. Schürch ◽  
Chiara Caraccio ◽  
Martijn A. Nolte
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Plasma Cells ◽  
Cell Types ◽  
Lymphoid Organ ◽  
Lymphoid Cells ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Mature Lymphocyte ◽  
Lymphocyte Populations

The bone marrow (BM) is responsible for generating and maintaining lifelong output of blood and immune cells. Besides its key hematopoietic function, the BM acts as an important lymphoid organ, hosting a large variety of mature lymphocyte populations, including B-cells, T-cells, NK(T)-cells and innate lymphoid cells (ILCs). Many of these cell types are thought to only transiently visit the BM, but for others, like plasma cells and memory T-cells, the BM provides supportive niches that promote their long-term survival. Interestingly, accumulating evidence points towards an important role for mature lymphocytes in the regulation of hematopoietic stem cells (HSCs) and hematopoiesis in health and disease. In this review, we describe the diversity, migration, localization and function of mature lymphocyte populations in murine and human BM, focusing on their role in immunity and hematopoiesis. We also address how various BM lymphocyte subsets contribute to the development of aplastic anemia and immune thrombocytopenia, illustrating the complexity of these BM disorders, but also the underlying similarities and differences in their disease pathophysiology. Finally, we summarize the interactions between mature lymphocytes and BM resident cells in HSC transplantation and graft-versus-host disease. A better understanding of the mechanisms by which mature lymphocyte populations regulate BM function will likely improve future therapies for patients with benign and malignant hematological disorders.

scholarly journals Bifurcation Analysis of an Age Structured HIV Infection Model with Both Virus-to-Cell and Cell-to-Cell Transmissions

2018 ◽  
Vol 28 (09) ◽  
pp. 1850109 ◽  
Author(s):  
Xiangming Zhang ◽  
Zhihua Liu
Keyword(s):  
T Cells ◽  
Hopf Bifurcation ◽  
Hiv Infection ◽  
Bifurcation Analysis ◽  
Dynamical Behavior ◽  
Infection Model ◽  
Positive Equilibrium ◽  
Semilinear Equations ◽  
Age Structured ◽  
Hiv Infection Model

We make a mathematical analysis of an age structured HIV infection model with both virus-to-cell and cell-to-cell transmissions to understand the dynamical behavior of HIV infection in vivo. In the model, we consider the proliferation of uninfected CD[Formula: see text] T cells by a logistic function and the infected CD[Formula: see text] T cells are assumed to have an infection-age structure. Our main results concern the Hopf bifurcation of the model by using the theory of integrated semigroup and the Hopf bifurcation theory for semilinear equations with nondense domain. Bifurcation analysis indicates that there exist some parameter values such that this HIV infection model has a nontrivial periodic solution which bifurcates from the positive equilibrium. The numerical simulations are also carried out.

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