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 Involvement of Fractalkine/CX3CL1 Expression by Dendritic Cells in the Enhancement of Host Immunity against Legionella pneumophila

2005 ◽  
Vol 73 (9) ◽  
pp. 5350-5357 ◽  
Author(s):  
Toshiaki Kikuchi ◽  
Sita Andarini ◽  
Hong Xin ◽  
Kazunori Gomi ◽  
Yutaka Tokue ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Host Defense ◽  
Legionella Pneumophila ◽  
Recombinant Adenovirus ◽  
Severe Pneumonia ◽  
Adenovirus Vector ◽  
Recombinant Adenovirus Vector ◽  
Legionnaires Disease

ABSTRACT Legionnaires' disease is clinically manifested as severe pneumonia caused by Legionella pneumophila. However, the dendritic cell (DC)-centered immunological framework of the host defense against L. pneumophila has not been fully delineated. For this study, we focused on a potent chemoattractant for lymphocytes, fractalkine/CX3CL1, and observed that the fractalkine expression of DCs was somewhat up-regulated when they encountered L. pneumophila. We therefore hypothesized that fractalkine expressed by Legionella-capturing DCs is involved in the induction of T-cell-mediated immune responses against Legionella, which would be enhanced by a genetic modulation of DCs to overexpress fractalkine. In vivo immunization-challenge experiments demonstrated that DCs modified with a recombinant adenovirus vector to overexpress fractalkine (AdFKN) and pulsed with heat-killed Legionella protected immunized mice from a lethal Legionella infection and that the generation of in vivo protective immunity depended on the host lymphocyte subsets, including CD4+ T cells, CD8+ T cells, and B cells. Consistent with this, immunization with AdFKN/Legionella/DC induced significantly higher levels of serum anti-Legionella antibodies of several isotypes than those induced by control immunizations. Further analysis of spleen cells from the immunized mice indicated that the AdFKN/Legionella/DC immunization elicited Th1-dominated immune responses to L. pneumophila. These observations suggest that fractalkine may play an important role in the DC-mediated host defense against intracellular pathogens such as L. pneumophila.

The liver as a crucial organ in the first line of host defense: the roles of Kupffer cells, natural killer (NK) cells and NK1.1 Ag+ T cells in T helper 1 immune responses

2000 ◽  
Vol 174 (1) ◽  
pp. 35-46 ◽  
Author(s):  
Shuhji Seki ◽  
Yoshiko Habu ◽  
Toshihiko Kawamura ◽  
Kazuyoshi Takeda ◽  
Hiroshi Dobashi ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Nk Cells ◽  
Natural Killer ◽  
Host Defense ◽  
Kupffer Cells ◽  
T Helper ◽  
T Helper 1 ◽  
First Line

Control of Immunity by the Microbiota

2021 ◽  
Vol 39 (1) ◽  
pp. 449-479
Author(s):  
Eduard Ansaldo ◽  
Taylor K. Farley ◽  
Yasmine Belkaid
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Microbial Communities ◽  
Adaptive Immunity ◽  
Immune Recognition ◽  
T Helper ◽  
Cell Responses ◽  
Temporal Windows

The immune system has coevolved with extensive microbial communities living on barrier sites that are collectively known as the microbiota. It is increasingly clear that microbial antigens and metabolites engage in a constant dialogue with the immune system, leading to microbiota-specific immune responses that occur in the absence of inflammation. This form of homeostatic immunity encompasses many arms of immunity, including B cell responses, innate-like T cells, and conventional T helper and T regulatory responses. In this review we summarize known examples of innate-like T cell and adaptive immunity to the microbiota, focusing on fundamental aspects of commensal immune recognition across different barrier sites. Furthermore, we explore how this cross talk is established during development, emphasizing critical temporal windows that establish long-term immune function. Finally, we highlight how dysregulation of immunity to the microbiota can lead to inflammation and disease, and we pinpoint outstanding questions and controversies regarding immune system–microbiota interactions.

scholarly journals Bifidobacterium bifidum Shows More Diversified Ways of Relieving Non-Alcoholic Fatty Liver Compared with Bifidobacterium adolescentis

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 84
Author(s):  
Linlin Wang ◽  
Ting Jiao ◽  
Qiangqing Yu ◽  
Jialiang Wang ◽  
Luyao Wang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Fatty Liver ◽  
Propionic Acid ◽  
Intestinal Permeability ◽  
Intestinal Microbiota ◽  
Relative Abundance ◽  
Bifidobacterium Bifidum ◽  
Liver Inflammation ◽  
Bifidobacterium Adolescentis ◽  
Alcoholic Fatty Liver

The occurrence of non-alcoholic fatty liver disease (NAFLD) is closely related to intestinal microbiota disturbance, and probiotics has become a new strategy to assist in alleviating NAFLD. In order to investigate the effect of Bifidobacterium on NAFLD and the possible pathway, a NAFLD model was established by using a high-fat diet (HFD) for 18 weeks. Fourteen strains of Bifidobacterium were selected (seven Bifidobacterium adolescentis and seven Bifidobacterium bifidum) for intervention. The effects of different bifidobacteria on NAFLD were evaluated from liver cell injury, liver fat deposition, liver inflammatory state and liver histopathology, and were taken as entry points to explore the mitigation approaches of bifidobacteria through energy intake, lipid metabolism, glucose metabolism and intestinal permeability. The results showed that Bifidobacterium exerts species-specific effects on NAFLD. B. bifidum exerted these effects mainly through regulating the intestinal microbiota, increasing the relative abundance of Faecalibaculum and Lactobacillus, decreasing the relative abundance of Tyzzerella, Escherichia-Shigella, Intestinimonas, Osillibacter and Ruminiclostridium, and further increasing the contents of propionic acid and butyric acid, regulating lipid metabolism and intestinal permeability, and ultimately inhibiting liver inflammation and fat accumulation to alleviate NAFLD. B. adolescentis exerted its effects mainly through changing the intestinal microbiota, increasing the content of propionic acid, regulating lipid metabolism and ultimately inhibiting liver inflammation to alleviate NAFLD.

scholarly journals Trichuris muris Model: Role in Understanding Intestinal Immune Response, Inflammation and Host Defense

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 925
Author(s):  
Yeganeh Yousefi ◽  
Sabah Haq ◽  
Suhrid Banskota ◽  
Yun Han Kwon ◽  
Waliul I. Khan
Keyword(s):  
Immune Responses ◽  
Host Defense ◽  
Intestinal Tract ◽  
Inflammatory Diseases ◽  
Intestinal Parasites ◽  
Intestinal Barrier ◽  
Parasitic Infections ◽  
Trichuris Muris ◽  
Host Parasite ◽  
Human Intestinal Tract

Several parasites have evolved to survive in the human intestinal tract and over 1 billion people around the world, specifically in developing countries, are infected with enteric helminths. Trichuris trichiura is one of the world’s most common intestinal parasites that causes human parasitic infections. Trichuris muris, as an immunologically well-defined mouse model of T. trichiura, is extensively used to study different aspects of the innate and adaptive components of the immune system. Studies on T. muris model offer insights into understanding host immunity, since this parasite generates two distinct immune responses in resistant and susceptible strains of mouse. Apart from the immune cells, T. muris infection also influences various components of the intestinal tract, especially the gut microbiota, mucus layer, epithelial cells and smooth muscle cells. Here, we reviewed the different immune responses generated by innate and adaptive immune components during acute and chronic T. muris infections. Furthermore, we discussed the importance of studying T. muris model in understanding host–parasite interaction in the context of alteration in the host’s microbiota, intestinal barrier, inflammation, and host defense, and in parasite infection-mediated modulation of other immune and inflammatory diseases.

Aryloxy Triester Phosphonamidates of Phosphoantigens Exhibit Favorable Stability and Potent Activation of Vγ9/Vδ2 T‐Cells

2018 ◽  
Author(s):  
Hachemi Kadri ◽  
Taher E. Taher ◽  
Qin Xu ◽  
Richard T. Bryan ◽  
Benjamin E. Willcox ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Serum Stability ◽  
T Cell Immune Responses ◽  
Further Development

We previously reported the application of the aryloxy triester phosphoramidate prodrug technology to the phosphoantigen (E)-4-hydroxybut-2-enyl phosphate (HMBP). Although these prodrugs exhibited potent activation of Vγ9/Vδ2 T‐cell immune responses, their stability was low due to the rapid cleavage of the -O-P- bond. To address this, we herein report the application of the same prodrug strategy to two HMBP phosphonates, which have stable -CH2-P- or -CF2-P- bonds. These HMBP phosphonate prodrugs, phosphonamidates, exhibited excellent serum stability and potent activation of Vgama9/Vdelta2 T‐cells making them attractive compounds for further development as potential immunotherapeutics.

Aryloxy Triester Phosphonamidates of Phosphoantigens Exhibit Favorable Stability and Potent Activation of Vγ9/Vδ2 T‐Cells

2018 ◽  
Author(s):  
Hachemi Kadri ◽  
Taher E. Taher ◽  
Qin Xu ◽  
Richard T. Bryan ◽  
Benjamin E. Willcox ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Serum Stability ◽  
T Cell Immune Responses ◽  
Further Development

We previously reported the application of the aryloxy triester phosphoramidate prodrug technology to the phosphoantigen (E)-4-hydroxybut-2-enyl phosphate (HMBP). Although these prodrugs exhibited potent activation of Vγ9/Vδ2 T‐cell immune responses, their stability was low due to the rapid cleavage of the -O-P- bond. To address this, we herein report the application of the same prodrug strategy to two HMBP phosphonates, which have stable -CH2-P- or -CF2-P- bonds. These HMBP phosphonate prodrugs, phosphonamidates, exhibited excellent serum stability and potent activation of Vgama9/Vdelta2 T‐cells making them attractive compounds for further development as potential immunotherapeutics.

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