Protective Immune Responses in The Intestinal Tract

2019 ◽  
pp. 143-198
Author(s):  
Timothy J. Newby
Keyword(s):  
Immune Responses ◽  
Intestinal Tract

scholarly journals 2262

2017 ◽  
Vol 1 (S1) ◽  
pp. 4-5
Author(s):  
Derrick Richard Samuelson ◽  
Vincent Maffei ◽  
Eugene Blanchard ◽  
Meng Luo ◽  
Christopher Taylor ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Microbial Communities ◽  
Intestinal Permeability ◽  
Intestinal Microbiota ◽  
Host Defense ◽  
Intestinal Tract ◽  
Liver Inflammation ◽  
Host Defenses ◽  
Increased Susceptibility

OBJECTIVES/SPECIFIC AIMS: Alcohol consumption perturbs the normal intestinal microbial communities (alcohol dysbiosis). To begin to investigate the relationship between alcohol-mediated dysbiosis and host defense we developed an alcohol dysbiosis fecal adoptive transfer model, which allows us to isolate the host immune response to a pathogenic challenge at a distal organ (ie, the lung). This model system allowed us to determine whether the host immune responses to Klebsiella pneumoniae are altered by ethanol-associated dysbiosis, independent of alcohol use. We hypothesized that alcohol-induced changes in intestinal microbial communities would impair pulmonary host defenses against K. pneumoniae. METHODS/STUDY POPULATION: Mice were treated with a cocktail of antibiotics daily for 2 weeks. Microbiota-depleted mice were then recolonized by gavage for 3-days with intestinal microbiota from ethanol-fed or pair-fed animals. Following recolonization groups of mice were sacrificed prior to and 48 hours post respiratory infection with K. pneumoniae. We then assessed susceptibility to Klebsiella infection by determining colony counts for pathogen burden in the lungs. We also determined lung and intestinal immunology, intestinal permeability, as well as, liver damage and inflammation. RESULTS/ANTICIPATED RESULTS: We found that increased susceptibility to K. pneumoniae is, in part, mediated by the intestinal microbiota, as animals recolonized with an alcohol-induced dysbiotic intestinal microbial community have significantly higher lung burdens of K. pneumoniae (5×104 CFU vs. 1×103 CFU) independent of EtOH. We also found that increased susceptibility in alcohol-dysbiosis recolonized animals was associated with a decrease in the recruitment and/or proliferation of CD4+ and CD8+ T-cells (1.5×109 cells vs. 2.5×109 cells) in the lung following Klebsiella infection. However, there were increased numbers of T-cells in the intestinal tract following Klebsiella infection, which may suggest that T cells are being sequestered in the intestinal tract to the detriment of host defense in the lung. Interestingly, mice recolonized with an alcohol-dysbiotic microbiota had increased intestinal permeability as measured by increased levels of serum intestinal fatty acid binding protein (55 vs. 30 ng/mL). Alcohol-dysbiotic microbiota also increased liver steatosis (Oil Red-O staining) and liver inflammation (>2-fold expression of IL-17 and IL-23). DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest that the commensal intestinal microbiota support mucosal host defenses against infectious agents by facilitating normal immune responses to pulmonary pathogens. Our data also suggest that increased intestinal permeability coupled with increased liver inflammation may impair the recruitment/proliferation of immune cells in the respiratory tract following infection. The role of the microbiota during host defense will be important areas of future research directed at understanding the effects of microbial dysbiosis in patients with AUDs.

scholarly journals THE LYMPHOID TISSUES AND IMMUNE RESPONSES OF NEONATALLY THYMECTOMIZED MICE BEARING THYMUS TISSUE IN MILLIPORE DIFFUSION CHAMBERS

1964 ◽  
Vol 119 (1) ◽  
pp. 177-194 ◽  
Author(s):  
David Osoba ◽  
J. F. A. P. Miller
Keyword(s):  
Immune Responses ◽  
Intestinal Tract ◽  
Lymphoid Cells ◽  
Lymphoid Tissues ◽  
Lymphoid Follicles ◽  
Diffusion Chambers ◽  
Wasting Syndrome ◽  
Thymus Tissue ◽  
Reticular Cells ◽  
Thymectomized Mice

Neonatally thymectomized mice were implanted intraperitoneally at 7 days of age with Millipore diffusion chambers containing either embryonic or neonatal thymus tissue. Mice which received either empty diffusion chambers or no further treatment following neonatal thymectomy served as controls. In contrast to these controls, most of the mice implanted with thymus-filled chambers gained weight satisfactorily, did not develop a wasting syndrome, and had the capacity to produce serum antibodies in response to sheep erythrocytes and to reject allogeneic skin grafts. Lymphoid follicles were present in the lymph nodes, spleen, and intestinal tract of the implanted mice but most still showed some diminution in the population of lymphocytes in both blood and tissues. Control thymectomized mice had markedly depleted lymphoid tissues and low peripheral blood lymphocyte levels. The tissue recovered after 1 to 2 months from the diffusion chambers showed only epithelial-reticular cells but no lymphoid cells. It is suggested that a humoral factor produced by the thymus epithelial-reticular complex may be responsible for endowing lymphoid cells with immunological competence.

scholarly journals Selection of Immunobiotic Ligilactobacillus salivarius Strains from the Intestinal Tract of Wakame-Fed Pigs: Functional and Genomic Studies

2020 ◽  
Vol 8 (11) ◽  
pp. 1659
Author(s):  
Binghui Zhou ◽  
Leonardo Albarracin ◽  
Yuhki Indo ◽  
Lorena Arce ◽  
Yuki Masumizu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Complete Genome ◽  
Intestinal Tract ◽  
Innate Immune ◽  
Comparative Genomic ◽  
Probiotic Properties ◽  
Innate Immune Responses ◽  
Selection Of

In this article, Ligilactobacillus salivarius FFIG strains, isolated from the intestinal tract of wakame-fed pigs, are characterized according to their potential probiotic properties. Strains were evaluated by studying their interaction with porcine intestinal epithelial (PIE) cells in terms of their ability to regulate toll-like receptor (TLR)-3- or TLR4-mediated innate immune responses, as well as by assessing their adhesion capabilities to porcine epithelial cells and mucins. These functional studies were complemented with comparative genomic evaluations using the complete genome sequences of porcine L. salivarius strains selected from subgroups that demonstrated different “immune” and “adhesion” phenotypes. We found that their immunomodulatory and adhesion capabilities are a strain-dependent characteristic. Our analysis indicated that the differential immunomodulatory and adhesive activities of FFIG strains would be dependent on the combination of several surface structures acting simultaneously, which include peptidoglycan, exopolysaccharides, lipoteichoic acid, and adhesins. Of note, our results indicate that there is no correlation between the immunomodulatory capacity of the strains with their adhesion ability to mucins and epithelial cells. Therefore, in the selection of strains destined to colonize the intestinal mucosa and modulate the immunity of the host, both properties must be adequately evaluated. Interestingly, we showed that L. salivarius FFIG58 functionally modulated the innate immune responses triggered by TLR3 and TLR4 activation in PIE cells and efficiently adhered to these cells. Moreover, the FFIG58 strain was capable of reducing rotavirus replication in PIE cells. Therefore, L. salivarius FFIG58 is a good candidate for further in vivo studying the protective effect of lactobacilli against intestinal infections in the porcine host. We also reported and analyzed, for the first time, the complete genome of several L. salivarius strains that were isolated from the intestine of pigs after the selective pressure of feeding the animals with wakame. Further genomic analysis could be of value to reveal the metabolic characteristics and potential of the FFIG strains in general and of the FFIG58 strain, in particular, relating to wakame by-products assimilation.

scholarly journals Microfluidic Device Using Mouse Small Intestinal Tissue for the Observation of Fluidic Behavior in the Lumen

Micromachines ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 692
Author(s):  
Satoru Kuriu ◽  
Naoyuki Yamamoto ◽  
Tadashi Ishida
Keyword(s):  
Small Intestine ◽  
Fluid Flow ◽  
Flow Field ◽  
Immune Responses ◽  
Microfluidic Device ◽  
Intestinal Tract ◽  
Gut Bacteria ◽  
Intestinal Tissue ◽  
Histological Techniques ◽  
Small Intestinal

The small intestine has the majority of a host’s immune cells, and it controls immune responses. Immune responses are induced by a gut bacteria sampling process in the small intestine. The mechanism of immune responses in the small intestine is studied by genomic or histological techniques after in vivo experiments. While the distribution of gut bacteria, which can be decided by the fluid flow field in the small intestinal tract, is important for immune responses, the fluid flow field has not been studied due to limits in experimental methods. Here, we propose a microfluidic device with chemically fixed small intestinal tissue as a channel. A fluid flow field in the small intestinal tract with villi was observed and analyzed by particle image velocimetry. After the experiment, the distribution of microparticles on the small intestinal tissue was histologically analyzed. The result suggests that the fluid flow field supports the settlement of microparticles on the villi.

scholarly journals Survey of Pathogen-Lowering and Immuno-Modulatory Effects Upon Treatment of Campylobacter coli-Infected Secondary Abiotic IL-10-/- Mice with the Probiotic Formulation Aviguard®

2021 ◽  
Vol 9 (6) ◽  
pp. 1127
Author(s):  
Dennis Weschka ◽  
Soraya Mousavi ◽  
Nina Biesemeier ◽  
Stefan Bereswill ◽  
Markus M. Heimesaat
Keyword(s):  
Immune Responses ◽  
Intestinal Tract ◽  
Clinical Signs ◽  
Campylobacter Coli ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Obligate Anaerobic ◽  
Intestinal Pathogen ◽  
Human Campylobacteriosis ◽  
Post Infectious

The prevalence of infections with the zoonotic enteritis pathogen Campylobacter coli is increasing. Probiotic formulations constitute promising antibiotic-independent approaches to reduce intestinal pathogen loads and modulate pathogen-induced immune responses in the infected human host, resulting in acute campylobacteriosis and post-infectious sequelae. Here, we address potential antipathogenic and immuno-modulatory effects of the commercial product Aviguard® during experimental campylobacteriosis. Secondary abiotic IL-10-/- mice were infected with a C. coli patient isolate on days 0 and 1, followed by oral Aviguard® treatment on days 2, 3 and 4. Until day 6 post-infection, Aviguard® treatment could lower the pathogen burdens within the proximal but not the distal intestinal tract. In contrast, the probiotic bacteria had sufficiently established in the intestines with lower fecal loads of obligate anaerobic species in C. coli-infected as compared to uninfected mice following Aviguard® treatment. Aviguard® application did not result in alleviated clinical signs, histopathological or apoptotic changes in the colon of infected IL-10-/- mice, whereas, however, Aviguard® treatment could dampen pathogen-induced innate and adaptive immune responses in the colon, accompanied by less distinct intestinal proinflammatory cytokine secretion. In conclusion, Aviguard® constitutes a promising probiotic compound to alleviate enteropathogen-induced proinflammatory immune responses during human campylobacteriosis.

scholarly journals Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism

2021 ◽  
Author(s):  
Hugo A Penny ◽  
Rita G Domingues ◽  
Maria Z Krauss ◽  
Felipe Melo-Gonzalez ◽  
Suzanna Dickson ◽  
...  
Keyword(s):  
Microbial Community ◽  
Immune Responses ◽  
Metabolic Activity ◽  
Intestinal Tract ◽  
Plasma Cells ◽  
Commensal Microbiota ◽  
Commensal Species ◽  
A Cell ◽  
Intestinal Iga ◽  
Diurnal Regulation

Mutualistic interactions with the commensal microbiota are enforced through a range of immune responses that confer metabolic benefits for the host and ensure tissue health and homeostasis. Immunoglobulin (Ig)A responses directly determine the composition of commensal species that colonize the intestinal tract but require significant metabolic resources to fuel antibody production by tissue-resident plasma cells. Here we demonstrate IgA responses are subject to diurnal regulation by dietary-derived metabolic cues and a cell-intrinsic circadian clock. Rhythmicity in IgA secretion conferred oscillatory patterns on the commensal microbial community and its associated metabolic activity, resulting in changes to metabolite availability over the course of the circadian day. Our findings suggest circadian networks comprising intestinal IgA, the diet and the microbiota align to ensure metabolic health.

scholarly journals Cutting Edge: Probiotics and Fecal Microbiota Transplantation in Immunomodulation

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Wenjie Zeng ◽  
Jie Shen ◽  
Tao Bo ◽  
Liangxin Peng ◽  
Hongbo Xu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Intestinal Tract ◽  
Recent Literature ◽  
Fecal Microbiota Transplantation ◽  
Treg Cells ◽  
Fecal Microbiota ◽  
T Helper ◽  
Beneficial Effects ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Probiotics are commensal or nonpathogenic microbes that confer beneficial effects on the host through several mechanisms such as competitive exclusion, antibacterial effects, and modulation of immune responses. Some probiotics have been found to regulate immune responses via immune regulatory mechanisms. T regulatory (Treg) cells, T helper cell balances, dendritic cells, macrophages, B cells, and natural killer (NK) cells can be considered as the most determinant dysregulated mediators in immunomodulatory status. Recently, fecal microbiota transplantation (FMT) has been defined as the transfer of distal gut microbial communities from a healthy individual to a patient’s intestinal tract to cure some immune disorders (mainly inflammatory bowel diseases). The aim of this review was followed through the recent literature survey on immunomodulatory effects and mechanisms of probiotics and FMT and also efficacy and safety of probiotics and FMT in clinical trials and applications.

scholarly journals Saccharomyces boulardii Modifies Salmonella Typhimurium Traffic and Host Immune Responses along the Intestinal Tract

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e103069 ◽  
Author(s):  
Rodolphe Pontier-Bres ◽  
Patrick Munro ◽  
Laurent Boyer ◽  
Rodolphe Anty ◽  
Véronique Imbert ◽  
...  
Keyword(s):  
Immune Responses ◽  
Salmonella Typhimurium ◽  
Intestinal Tract ◽  
Saccharomyces Boulardii ◽  
Host Immune Responses

scholarly journals Immune-modulatory Properties of the Octapeptide NAP in Campylobacter jejuni Infected Mice Suffering from Acute Enterocolitis

2020 ◽  
Vol 8 (6) ◽  
pp. 802 ◽  
Author(s):  
Markus M. Heimesaat ◽  
Soraya Mousavi ◽  
Sigri Kløve ◽  
Claudia Genger ◽  
Dennis Weschka ◽  
...  
Keyword(s):  
Immune Responses ◽  
Campylobacter Jejuni ◽  
Post Infection ◽  
Intestinal Tract ◽  
Clinical Signs ◽  
Global Public Health ◽  
Food Borne ◽  
Human Infections ◽  
First Time ◽  
Post Infectious

Human infections with the food-borne zoonotic pathogen Campylobacter jejuni are progressively rising and constitute serious global public health and socioeconomic burdens. Hence, application of compounds with disease-alleviating properties are required to combat campylobacteriosis and post-infectious sequelae. In our preclinical intervention study applying an acute C. jejuni induced enterocolitis model, we surveyed the anti-pathogenic and immune-modulatory effects of the octapeptide NAP which is well-known for its neuroprotective and anti-inflammatory properties. Therefore, secondary abiotic IL-10−/− mice were perorally infected with C. jejuni and intraperitoneally treated with synthetic NAP from day 2 until day 5 post-infection. NAP-treatment did not affect gastrointestinal C. jejuni colonization but could alleviate clinical signs of infection that was accompanied by less pronounced apoptosis of colonic epithelial cells and enhancement of cell regenerative measures on day 6 post-infection. Moreover, NAP-treatment resulted in less distinct innate and adaptive pro-inflammatory immune responses that were not restricted to the intestinal tract but could also be observed in extra-intestinal and even systemic compartments. NAP-treatment further resulted in less frequent translocation of viable pathogens from the intestinal tract to extra-intestinal including systemic tissue sites. For the first time, we here provide evidence that NAP application constitutes a promising option to combat acute campylobacteriosis.

scholarly journals A Novel Bacterium-Like Particle Vaccine Displaying the MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and Systemic Immune Responses in Mice

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 799 ◽  
Author(s):  
Li ◽  
Chi ◽  
Huang ◽  
Yan ◽  
Zhang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Receptor Binding ◽  
Fusion Proteins ◽  
Intestinal Tract ◽  
Binding Activity ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Respiratory Illnesses ◽  
Novel Bacterium ◽  
And Control

Middle East respiratory syndrome coronavirus (MERS-CoV), a new coronavirus that has been causing severe and fatal acute respiratory illnesses in humans since its outbreak in 2012, has raised public fear worldwide. The development of prophylactics and therapeutics is urgently needed to prevent and control MERS-CoV infections. In this study, a bacterium (Lactococcus lactis)-like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). The designs included different numbers of lysin motif (LysM) repeats in the PAs linked by linkers (RBD-linker-PA2 (RLP2), RBD-linker-PA3 (RLP3) and RBD-PA3 (RP3)), and three LysM repeats and a linker in the fusion proteins increased the binding activity to the RBD. The specific immune responses were tested by intranasally immunizing mice with RLP3-GEM with or without the adjuvant GEL01. The results showed that GEL01-adjuvanted RLP3-GEM increased the systemic humoral, cellular and local mucosal immune responses in the mouse model, especially in the intestinal tract. The above results indicate that the MERS-CoV BLP product has the potential to be developed into a promising mucosal candidate vaccine to protect against MERS-CoV infections.

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