scholarly journals Microbiota composition and inflammatory immune responses upon peroral application of the commercial competitive exclusion product Aviguard® to microbiota-depleted wildtype mice

2020 ◽  
Vol 10 (3) ◽  
pp. 139-146
Author(s):  
Markus M. Heimesaat ◽  
Dennis Weschka ◽  
Sigri Kløve ◽  
Claudia Genger ◽  
Nina Biesemeier ◽  
...  
Keyword(s):  
Immune Responses ◽  
Competitive Exclusion ◽  
Immune Cell ◽  
Bacterial Colonization ◽  
Clinical Signs ◽  
Feed Additives ◽  
Bacterial Strains ◽  
Cell Responses ◽  
Adaptive Immune Cells ◽  
Pre Treatment

AbstractNon-antibiotic feed additives including competitive exclusion products have been shown effective in reducing pathogen loads including multi-drug resistant strains from the vertebrate gut. In the present study we surveyed the intestinal bacterial colonization properties, potential macroscopic and microscopic inflammatory sequelae and immune responses upon peroral application of the commercial competitive exclusion product Aviguard® to wildtype mice in which the gut microbiota had been depleted by antibiotic pre-treatment. Until four weeks following Aviguard® challenge, bacterial strains abundant in the probiotic suspension stably established within the murine intestines. Aviguard® application did neither induce any clinical signs nor gross macroscopic intestinal inflammatory sequelae, which also held true when assessing apoptotic and proliferative cell responses in colonic epithelia until day 28 post-challenge. Whereas numbers of colonic innate immune cell subsets such as macrophages and monocytes remained unaffected, peroral Aviguard® application to microbiota depleted mice was accompanied by decreases in colonic mucosal counts of adaptive immune cells such as T and B lymphocytes. In conclusion, peroral Aviguard® application results i.) in effective intestinal colonization within microbiota depleted mice, ii.) neither in macroscopic nor in microscopic inflammatory sequelae and iii.) in lower colonic mucosal T and B cell responses.

scholarly journals Zoonotic Vaccinia Viruses Belonging to Different Genetic Clades Exhibit Immunomodulation Abilities That Are Proportional to Their Pathogenic Potential

2021 ◽  
Author(s):  
Karine Lima Lourenço ◽  
Leandro Andrade Chinália ◽  
Lethícia Rodrigues Henriques ◽  
Rodrigo Araújo Lima Rodrigues ◽  
Flávio Guimarães da Fonseca
Keyword(s):  
Immune Responses ◽  
Immune Cell ◽  
Clinical Signs ◽  
Lung Damage ◽  
Pathogenic Potential ◽  
Cell Responses ◽  
Vaccinia Viruses ◽  
Group 2

Abstract BackgroundThe Vaccinia virus (VACV) isolates, Guarani P1 virus (GP1V) and Passatempo virus (PSTV), were isolated from zoonotic outbreaks in Brazil and belong to two different VACV clades, as defined by biological aspects that include virulence in mice and phylogenetic analysis. Considering that information about how vaccinia viruses from different groups elicit immune responses in animals is scarce, we investigated such responses in mice infected by GP1V (group 2) or PSTV (group 1) using VACV Western Reserve strain (WR) as control. MethodsThe severity of the infections was evaluated in BALB/c mice considering diverse clinical signs and defined scores, and the immune responses triggered by GP1V and PSTV infections were analysed by immune cell phenotyping and intra-cytoplasmic cytokines detection. ResultsInfected mice showed significant weight loss and developed spleen lesions as well as liver and lung damage. Mice infected with PSTV, however, developed only moderate clinical signs. We detected a reduction of total lymphocytes (CD3+), macrophages (CD14+) and NK cells (CD3-CD49+) in animals infected with VACV-WR or GP1V. VACV-WR was able to significantly downmodulate cell immune responses upon mice infection, and GP1V-infected animals also showed intense downmodulation in cell responses. Contrarily, PSTV presented little ability to downmodulate mice immune responses. ConclusionsOur results suggest that VACV immunomodulation in vivo is clade-related and is proportional to the strain virulence upon infection. Our data corroborate the classification of the different Brazilian VACV isolates in clades 1 and 2, taking into account not only phylogenetic criteria, but also clinical and immunological data.

scholarly journals Toll-Like Receptor-4 Is Involved in Mediating Intestinal and Extra-Intestinal Inflammation in Campylobacter coli-Infected Secondary Abiotic IL-10−/− Mice

2020 ◽  
Vol 8 (12) ◽  
pp. 1882
Author(s):  
Sigri Kløve ◽  
Claudia Genger ◽  
Dennis Weschka ◽  
Soraya Mousavi ◽  
Stefan Bereswill ◽  
...  
Keyword(s):  
Immune Responses ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Intestinal Inflammation ◽  
Clinical Signs ◽  
Campylobacter Coli ◽  
Toll Like Receptor ◽  
Host Interactions ◽  
Non Invasive ◽  
Health Burdens

Human Campylobacter infections are emerging worldwide and constitute significant health burdens. We recently showed that the immunopathological sequelae in Campylobacter jejuni-infected mice were due to Toll-like receptor (TLR)-4 dependent immune responses induced by bacterial lipooligosaccharide (LOS). Information regarding the molecular mechanisms underlying Campylobacter coli-host interactions are scarce, however. Therefore, we analyzed C. coli-induced campylobacteriosis in secondary abiotic IL-10−/− mice with and without TLR4. Mice were infected perorally with a human C. coli isolate or with a murine commensal Escherichia coli as apathogenic, non-invasive control. Independent from TLR4, C. coli and E. coli stably colonized the gastrointestinal tract, but only C. coli induced clinical signs of campylobacteriosis. TLR4−/− IL-10−/− mice, however, displayed less frequently fecal blood and less distinct histopathological and apoptotic sequelae in the colon versus IL-10−/− counterparts on day 28 following C. coli infection. Furthermore, C. coli-induced colonic immune cell responses were less pronounced in TLR4−/− IL-10−/− as compared to IL-10−/− mice and accompanied by lower pro-inflammatory mediator concentrations in the intestines and the liver of the former versus the latter. In conclusion, our study provides evidence that TLR4 is involved in mediating C. coli-LOS-induced immune responses in intestinal and extra-intestinal compartments during murine campylobacteriosis.

scholarly journals Mapping and Characterization of HCMV-Specific Unconventional HLA-E-Restricted CD8 T Cell Populations and Associated NK and T Cell Responses Using HLA/Peptide Tetramers and Spectral Flow Cytometry

2021 ◽  
Vol 23 (1) ◽  
pp. 263
Author(s):  
Amélie Rousselière ◽  
Laurence Delbos ◽  
Céline Bressollette ◽  
Maïlys Berthaume ◽  
Béatrice Charreau
Keyword(s):  
Flow Cytometry ◽  
T Cell ◽  
Immune Responses ◽  
Nk Cells ◽  
Hcmv Infection ◽  
Immune Cell ◽  
Nk Cell ◽  
Spectral Flow ◽  
Cell Responses

HCMV drives complex and multiple cellular immune responses, which causes a persistent immune imprint in hosts. This study aimed to achieve both a quantitative determination of the frequency for various anti-HCMV immune cell subsets, including CD8 T, γδT, NK cells, and a qualitative analysis of their phenotype. To map the various anti-HCMV cellular responses, we used a combination of three HLApeptide tetramer complexes (HLA-EVMAPRTLIL, HLA-EVMAPRSLLL, and HLA-A2NLVPMVATV) and antibodies for 18 surface markers (CD3, CD4, CD8, CD16, CD19, CD45RA, CD56, CD57, CD158, NKG2A, NKG2C, CCR7, TCRγδ, TCRγδ2, CX3CR1, KLRG1, 2B4, and PD-1) in a 20-color spectral flow cytometry analysis. This immunostaining protocol was applied to PBMCs isolated from HCMV- and HCMV+ individuals. Our workflow allows the efficient determination of events featuring HCMV infection such as CD4/CD8 ratio, CD8 inflation and differentiation, HCMV peptide-specific HLA-EUL40 and HLA-A2pp65CD8 T cells, and expansion of γδT and NK subsets including δ2-γT and memory-like NKG2C+CD57+ NK cells. Each subset can be further characterized by the expression of 2B4, PD-1, KLRG1, CD45RA, CCR7, CD158, and NKG2A to achieve a fine-tuned mapping of HCMV immune responses. This assay should be useful for the analysis and monitoring of T-and NK cell responses to HCMV infection or vaccines.

scholarly journals Zoonotic vaccinia virus strains belonging to different genetic clades exhibit immunomodulation abilities that are proportional to their virulence

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Karine Lima Lourenço ◽  
Leandro Andrade Chinália ◽  
Lethícia Ribeiro Henriques ◽  
Rodrigo Araújo Lima Rodrigues ◽  
Flávio Guimarães da Fonseca
Keyword(s):  
Immune Responses ◽  
Vaccinia Virus ◽  
Murine Model ◽  
Immune Cell ◽  
Clinical Signs ◽  
Vaccinia Viruses ◽  
Biological Aspects ◽  
Group 2

Abstract Background The vaccinia virus (VACV) isolates, Guarani P1 virus (GP1V) and Passatempo virus (PSTV), were isolated during zoonotic outbreaks in Brazil. Each one of them belongs to two different VACV clades, defined by biological aspects that include virulence in mice and phylogenetic analysis. Considering that information about how vaccinia viruses from different groups elicit immune responses in animals is scarce, we investigated such responses in mice infected either by GP1V (group 2) or PSTV (group 1), using VACV Western Reserve strain (VACV-WR) as control. Methods The severity of the infections was evaluated in BALB/c mice considering diverse clinical signs and defined scores, and the immune responses triggered by GP1V and PSTV infections were analysed by immune cell phenotyping and intra-cytoplasmic cytokines detection. Results We detected a reduction in total lymphocytes (CD3 +), macrophages (CD14 +), and NK cells (CD3-CD49 +) in animals infected with VACV-WR or GP1V. The VACV-WR and GP1V viruses, belonging to the most virulent group in a murine model, were able to down-modulate the cell immune responses upon mice infection. In contrast, PSTV, a virus considered less virulent in a murine model, showed little ability to down-modulate the mice immune responses. Mice infected with VACV-WR and GP1V viruses presented significant weight loss and developed lesions in their spleens, as well as damage to liver and lungs whereas mice infected with PSTV developed only moderate clinical signs. Conclusions Our results suggest that VACV immunomodulation in vivo is clade-related and is proportional to the strain’s virulence upon infection. Our data corroborate the classification of the different Brazilian VACV isolates into clades 1 and 2, taking into account not only phylogenetic criteria, but also clinical and immunological data.

scholarly journals Radiofrequency Ablation of Liver Metastases from Colorectal Cancer Induces a Cancer-Specific T Cell Repertoire in Humans

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1120-1120
Author(s):  
Markus W. Loeffler ◽  
Bianca Nussbaum ◽  
Philipp S. Jurmeister ◽  
Jan Budczies ◽  
Daniel Johannes Kowalewski ◽  
...  
Keyword(s):  
T Cells ◽  
Radiofrequency Ablation ◽  
T Cell ◽  
Immune Responses ◽  
Tumor Antigens ◽  
Immune Cell ◽  
Cell Responses ◽  
Hla Ligand ◽  
Hla Ligands ◽  
Immune Cell Infiltrates

Abstract Introduction: For patients with otherwise non-resectable primary and secondary cancer manifestations within the liver or contraindications against surgery, radiofrequency ablation (RFA) is a potentially curative treatment option. Heat causes coagulative necrosis and breaks local immune tolerance with subsequent release of cellular content like soluble danger signals which may reshape adaptive anti-tumor immune responses. The induction of effective functional tumor-specific T cells and in situ tumor-recognition remain a major challenge for immunotherapy, frequently limiting therapeutic effects. In this study, the induction of antigen-specific T cells against patient-individual, naturally presented tumor antigens and the infiltration of immune cells into distant liver metastasis after RFA were evaluated. Methods: Six patients suffering from at least two metastatic sites in different liver lobes derived from colorectal carcinoma (CRC) were enrolled. As an initial step, RFA was performed on those manifestations that were inaccessible by surgery. Patients subsequently underwent liver surgery of the residual metastases. These specimen were used for HLA-ligandome analyses of tumor and corresponding non-malignant liver (NML) tissues by uHPLC-coupled tandem mass spectrometry (MS) following HLA-immunoprecipitation. The identified naturally presented HLA-ligands were screening against an extensive HLA-ligand database containing data from non-malignant tissues from different origins to assess tumor specificity of single peptides. Further, whole transcriptome sequencing (WTS) was performed and correlated with MS data selecting HLA-ligands of interest. Functional T cell reactivity against selected antigens was analyzed by intracellular cytokine staining (ICS). Immune cell infiltrates of surgically resected liver metastases were assessed by immunohistochemistry staining (IHC including antibodies specific for CD3, CD4, CD8, CD56, HLA class I and II, and heat shock protein 70) in 11 and 5 patients undergoing hemihepatectomy with or without previous RFA, respectively. Results: 32 tumor-exclusive T cell epitope candidates were selected based on WTS and ligandome analyses. Antigen-specific T cells were detected in all included patients at least at one timepoint (including boosting of preexisting immune responses and de novo induction). Of note, one patient exhibited RFA-mediated induction of antigen-specific CD4+ T cells against one mutation-derived HLA-class II peptide. This epitope was predicted on the basis of the WST data, but could not be corroborated in MS data as a naturally presented HLA-ligand. Immunohistochemistry of immune cell infiltrates in the lesions resected after RFA did not reveal any significantly increased immune infiltrates in RFA pre-treated patients as compared to the control group. Conclusions: Specific T cell responses directed against tumor-antigens were detected in every patient investigated. Most notably, T cell responses were boosted or induced in 3 out of 6 patients following RFA, including in one patient against a tumor-specific neoantigen. Still, this tumor-specific immunity per se is probably insufficient to eradicate established tumors. This is underlined by the observation that no increased immune infiltrates in distant metastases were shown. Therefore, our findings support the clinical development of combinatorial therapies, combining RFA with suitable immune stimulatory agents. Disclosures Kowalewski: Immatics Biotechnologies GmbH: Employment.

scholarly journals IL-15 re-programming compensates for NK cell mitochondrial dysfunction in HIV-1 infection

2019 ◽  
Author(s):  
Elia Moreno Cubero ◽  
Stefan Balint ◽  
Aljawharah Alrubayyi ◽  
Ane Ogbe ◽  
Rebecca Matthews ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Nk Cells ◽  
Cell Function ◽  
Immune Cell ◽  
Nk Cell ◽  
Mammalian Target Of Rapamycin ◽  
Dynamic Regulation ◽  
Cell Responses ◽  
Pre Treatment ◽  
Hiv 1

AbstractDynamic regulation of cellular metabolism is important for maintaining homeostasis and can directly influence immune cell function and differentiation including Natural Killer (NK) cell responses. Persistent HIV-1 infection leads to a state of chronic activation, subset redistribution and progressive NK cell dysregulation. In this study we examined the metabolic processes that characterise NK cell subsets in HIV-1 infection, including adaptive NK cell subpopulations expressing the activating receptor NKG2C, which expand during chronic infection. These adaptive NK cells exhibit an enhanced metabolic profile in human cytomegalovirus (HCMV) infected HIV-1 seronegative individuals. However, the bioenergetic advantage of adaptive CD57+NKG2C+ NK cells is diminished during chronic HIV-1 infection, where NK cells uniformly display reduced oxidative phosphorylation (OXPHOS) and limited fuel flexibility upon CD16 stimulation. Defective OXPHOS was accompanied by increased mitochondrial depolarisation and structural alterations indicative of mitochondrial dysfunction, suggesting that mitochondrial defects are restricting the metabolic plasticity of NK cell subsets in HIV-1 infection. The metabolic requirement for receptor stimulation was alleviated upon IL-15 pre-treatment enhancing mammalian target of rapamycin complex1 (mTORC1) activity and NK cell functionality in HIV-1 infection, representing an effective strategy for pharmacologically boosting NK cell responses.

scholarly journals Immunotherapy of Cancer: Reprogramming Tumor-Immune Crosstalk

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Kyle K. Payne ◽  
Amir A. Toor ◽  
Xiang-Yang Wang ◽  
Masoud H. Manjili
Keyword(s):  
Immune Responses ◽  
Cancer Immunotherapy ◽  
Immune Cell ◽  
Tumor Escape ◽  
Aberrant Expression ◽  
Adaptive Immune ◽  
Cancer Testis Antigens ◽  
Adaptive Immune Cells ◽  
Immunotherapy Of Cancer ◽  
Cell Crosstalk

The advancement of cancer immunotherapy faces barriers which limit its efficacy. These include weak immunogenicity of the tumor, as well as immunosuppressive mechanisms which prevent effective antitumor immune responses. Recent studies suggest that aberrant expression of cancer testis antigens (CTAs) can generate robust antitumor immune responses, which implicates CTAs as potential targets for immunotherapy. However, the heterogeneity of tumor cells in the presence and quantity of CTA expression results in tumor escape from CTA-specific immune responses. Thus, the ability to modulate the tumor cell epigenome to homogenously induce expression of such antigens will likely render the tumor more immunogenic. Additionally, emerging studies suggest that suppression of antitumor immune responses may be overcome by reprogramming innate and adaptive immune cells. Therefore, this paper discusses recent studies which address barriers to successful cancer immunotherapy and proposes a strategy of modulation of tumor-immune cell crosstalk to improve responses in carcinoma patients.

scholarly journals Efficacy of medium-chain fatty acid salts distilled from coconut oil against two enteric pathogen challenges in weanling piglets

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Paola López-Colom ◽  
Lorena Castillejos ◽  
Agustina Rodríguez-Sorrento ◽  
Mónica Puyalto ◽  
Juan José Mallo ◽  
...  
Keyword(s):  
Immune Cell ◽  
Clinical Signs ◽  
Coconut Oil ◽  
Feed Additives ◽  
Intestinal Morphology ◽  
Rrna Gene ◽  
Post Inoculation ◽  
Fermentation Products ◽  
Medium Chain ◽  
Colonic Microbiota

Abstract Background The search for alternatives to antibiotics in pig production has increased the interest in natural resources with antimicrobial properties, such as medium-chain fatty acids (MCFA) as in-feed additives. This study evaluated the potential of a novel blend of MCFA salts (DIC) from distilled coconut oil with a lauric acid content to reduce enteropathogens and control intestinal diseases around weaning. Two experimental disease models were implemented in early-weaned piglets, consisting of two oral challenges: Salmonella Typhimurium (1.2 × 108 CFU) or enterotoxigenic Escherichia coli (ETEC) F4 (1.5 × 109 CFU). The parameters assessed were: animal performance, clinical signs, pathogen excretion, intestinal fermentation, immune-inflammatory response, and intestinal morphology. Results The Salmonella challenge promoted an acute course of diarrhea, with most of the parameters responding to the challenge, whereas the ETEC F4 challenge promoted a mild clinical course. A consistent antipathogenic effect of DIC was observed in both trials in the hindgut, with reductions in Salmonella spp. plate counts in the cecum (P = 0.03) on d 8 post-inoculation (PI) (Salmonella trial), and of enterobacteria and total coliform counts in the ileum and colon (P < 0.10) on d 8 PI (ETEC F4 trial). When analyzing the entire colonic microbiota (16S rRNA gene sequencing), this additive tended (P = 0.13) to reduce the Firmicutes/Bacteroidetes ratio and enriched Fibrobacteres after the Salmonella challenge. In the ETEC F4 challenge, DIC prompted structural changes in the ecosystem with increases in Dialister, and a trend (P = 0.14) to increase the Veillonellaceae family. Other parameters such as the intestinal fermentation products or serum pro-inflammatory mediators were not modified by DIC supplementation, nor were the histological parameters. Only the intraepithelial lymphocyte (IEL) counts were lowered by DIC in animals challenged with Salmonella (P = 0.07). With ETEC F4, the IEL counts were higher with DIC on d 8 PI (P = 0.08). Conclusions This study confirms the potential activity of this MCFA salts mixture to reduce intestinal colonization by opportunistic pathogens such as Salmonella or E. coli and its ability to modulate colonic microbiota. These changes could explain to some extent the local immune cell response at the ileal level.

scholarly journals Fatty acids and immune function: new insights into mechanisms

2007 ◽  
Vol 98 (S1) ◽  
pp. S41-S45 ◽  
Author(s):  
Parveen Yaqoob ◽  
Philip C. Calder
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Immune Responses ◽  
Cell Activation ◽  
Inflammatory Mediator ◽  
Immune Cell ◽  
Structural Components ◽  
Immune Cell Activation ◽  
Cell Responses ◽  
Inflammatory Mediator Production

Fatty acids are known to play diverse roles in immune cells. They are important as a source of energy, as structural components of cell membranes, as signaling molecules and as precursors for the synthesis of eicosanoids and similar mediators. Recent research has suggested that the localization and organisation of fatty acids into distinct cellular pools has a direct influence on the behaviour of a number of proteins involved in immune cell activation, including those associated with T cell responses, antigen presentation and fatty acid-derived inflammatory mediator production. This article reviews these studies and places them in the context of existing literature in the field. These studies indicate the existence of several novel mechanisms by which altered fatty acid availability can modulate immune responses and impact upon clinical outcomes.

scholarly journals Toll-Like Receptor-4 Dependent Intestinal and Systemic Sequelae Following Peroral Campylobacter coli Infection of IL10 Deficient Mice Harboring a Human Gut Microbiota

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 386 ◽  
Author(s):  
Sigri Kløve ◽  
Claudia Genger ◽  
Soraya Mousavi ◽  
Dennis Weschka ◽  
Stefan Bereswill ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Responses ◽  
Immune Cell ◽  
Fecal Microbiota Transplantation ◽  
Clinical Signs ◽  
Toll Like Receptor ◽  
Human Gut ◽  
Toll Like Receptor 4 ◽  
Host Immune Responses ◽  
Human Gut Microbiota

Zoonotic Campylobacter, including C. jejuni and C. coli, are among the most prevalent agents of food-borne enteritis worldwide. The immunopathological sequelae of campylobacteriosis are caused by Toll-like Receptor-4 (TLR4)-dependent host immune responses, induced by bacterial lipooligosaccharide (LOS). In order to investigate C. coli-host interactions, including the roles of the human gut microbiota and TLR4, upon infection, we applied a clinical acute campylobacteriosis model, and subjected secondary abiotic, TLR4-deficient IL10-/- mice and IL10-/- controls to fecal microbiota transplantation derived from human donors by gavage, before peroral C. coli challenge. Until day 21 post-infection, C. coli could stably colonize the gastrointestinal tract of human microbiota-associated (hma) mice of either genotype. TLR4-deficient IL10-/- mice, however, displayed less severe clinical signs of infection, that were accompanied by less distinct apoptotic epithelial cell and innate as well as adaptive immune cell responses in the colon, as compared to IL10-/- counterparts. Furthermore, C. coli infected IL10-/-, as opposed to TLR4-deficient IL10-/-, mice displayed increased pro-inflammatory cytokine concentrations in intestinal and, strikingly, systemic compartments. We conclude that pathogenic LOS might play an important role in inducing TLR4-dependent host immune responses upon C. coli infection, which needs to be further addressed in more detail.

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