• IMMUNE NETWORK
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• v.22 no.1
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• pp.3.1-3.21
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• 2022

Cancer is one of the leading causes of death worldwide and the number of cancer patients is expected to continuously increase in the future. Traditional cancer therapies focus on inhibiting cancer growth while largely ignoring the contribution of the immune system in eliminating cancer cells. Recently, better understanding of immunological mechanisms pertaining to cancer progress has led to development of several immunotherapies, which revolutionized cancer treatment. Nonetheless, only a small proportion of cancer patients respond to immunotherapy and maintain a durable response. Among multiple factors contributing to the variability of immunotherapy response rates, commensal microbiota inhabiting patients have been identified as one of the most critical factors determining the success of immunotherapy. The functional diversity of microbiota differentially affects the host immune system and controls the efficacy of immunotherapy in individual cancer patients. Moreover, clinical studies have demonstrated that changing the gut microbiota composition by fecal microbiota transplantation in patients who failed a previous immunotherapy converts them to responders of the same therapy. Consequently, both academic and industrial researchers are putting extensive efforts to identify and develop specific bacteria or bacteria mixtures for cancer immunotherapy. In this review, we will summarize the immunological roles of commensal microbiota in cancer treatment and give specific examples of bacteria that show anticancer effect when administered as a monotherapy or as an adjuvant agent for immunotherapy. We will also list ongoing clinical trials testing the anticancer effect of commensal bacteria.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.12 no.2
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• pp.140-149
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• 2009

Purpose: Helicobacter pylori infection is probably acquired in childhood and persists as an asymptomatic infection for decades in most individuals. It is unclear why only a minority of those infected develop a clinical manifestation, even in childhood, such as peptic ulcer disease. H. pylori infection activates local immune responses and causes lymphocyte infiltration in the gastric mucosa. We have previously reported that both T and B cells in the lamina propria play important roles in the local immune response of H. pylori-infected children. The aim of this study was to investigate the association between H. pylori genotypes and gastric mucosal lymphocytes. Methods: Twenty-five H. pylori-infected children (10 with peptic ulcer disease and 15 with gastritis) were enrolled in this study. We investigated the genotypes (cagA, cagE, vacA, and babA2) and evaluated the association with clinical manifestations, histopathology, and gastric mucosal lymphocytes. Results: The prevalence of cagA, cagE, vacA s1m1, and babA2 was 80%, 60%, 84%, and 88%, respectively. The most prevalent (68%) combination of cagA, vacA, and babA2 genotypes was cagA+/vacA s1m1+/babA2+. H. pylori genotypes were not associated with clinical manifestations, histopathology, or gastric mucosal lymphocytes. Conclusion: There was no association between the cagA, cagE, vacA, or babA2 status and gastric mucosal lymphocytes. The role of the host immune response in relation to H. pylori genotypes and disease potential in children needs further studies.

• The Journal of Korean Academy of Prosthodontics
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• v.29 no.2
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• pp.211-223
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• 1991

This study was aimed to observe the histological changes of the edentulous and denture wearing alveolar ridge mucosa. The distribution of Langerhans cells was also observed to investigate the mucosal immune response by denture wearing. The mucosal tissues were obtained from of 12 cases of edentulous nondenture wearers(NDW), 7 cases of denture wearers(DW), and 12 cases of flabby tissues(FT). For the identification of Langerhans cells of the mucosal epithelia, the immunohistochemical stain for S-100 protein was applied. The results were as follows : 1. 7 cases among 12 cases of NDW showed hyperkeratosis, and 5 cases were covered by parakeratosis, whereas 3 cases among 7 cases of DW showed hyperkeratosis, and 4 cases showed parakeratosis on the mucosal epithelium. All cases of both DW and NDW demonstrated epithelial hyperplasia, except. 2 cases of DW, which showed epithelial atrophy. The content of glycogen in the epithelial layer showed the decrease in the group of DW. 2. Both NDW and DW showed the infiltration of chronic inflammatory cells. The collagen fibers tended to be arranged densely and irregularly in cases of denture wearing period more than 10 years. 3. FT showed variable epithelial changes from epithelial atrophy to marked hyperplasia, and the pattern of keratinization was also variable. The collagen fibers tended to be arranged irregularly. 4. The distribution of Langerhans cells showed the increase of 1.84-1.96 times in the group of DW compared with NDW group.

• IMMUNE NETWORK
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• v.15 no.2
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• pp.73-82
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• 2015

Respiratory syncytial virus (RSV) infection is recognized by the innate immune system through Toll like receptors (TLRs) and retinoic acid inducible gene I. These pathways lead to the activation of type I interferons and resistance to infection. In contrast to TLRs, very few studies have examined the role of NOD-like receptors in viral recognition and induction of adaptive immune responses to RSV. Caspase-1 plays an essential role in the immune response via the maturation of the proinflammatory cytokines IL-$1{\beta}$ and IL-18. However, the role of caspase-1 in RSV infection in vivo is unknown. We demonstrate that RSV infection induces IL-$1{\beta}$ secretion and that caspase-1 deficiency in bone marrow derived dendritic cells leads to defective IL-$1{\beta}$ production, while normal RSV viral clearance and T cell responses are observed in caspase-1 deficient mice following respiratory infection with RSV. The frequencies of IFN-${\gamma}$ producing or RSV specific T cells in lungs from caspase-1 deficient mice are not impaired. In addition, we demonstrate that caspase-1 deficient neonatal or young mice also exhibit normal immune responses. Furthermore, we find that IL-1R deficient mice infected with RSV exhibit normal Th1 and cytotoxic T lymphocytes (CTL) immune responses. Collectively, these results demonstrate that in contrast to TLR pathways, caspase-1 might not play a central role in the induction of Th1 and CTL immune responses to RSV.

• Journal of Yeungnam Medical Science
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• v.38 no.1
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• pp.27-33
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• 2021

The gut is a complex organ that has played an important role in digestion, absorption, endocrine functions, and immunity. The gut mucosal barriers consist of the immunologic barrier and nonimmunologic barrier. During critical illnesses, the gut is susceptible to injury due to the induction of intestinal hyperpermeability. Gut hyperpermeability and barrier dysfunction may lead to systemic inflammatory response syndrome. Additionally, gut microbiota are altered during critical illnesses. The etiology of such microbiome alterations in critical illnesses is multifactorial. The interaction or systemic host defense modulation between distant organs and the gut microbiome is increasingly studied in disease research. No treatment modality exists to significantly enhance the gut epithelial integrity, permeability, or mucus layer in critically ill patients. However, multiple helpful approaches including clinical and preclinical strategies exist. Enteral nutrition is associated with an increased mucosal barrier in animal and human studies. The trophic effects of enteral nutrition might help to maintain the intestinal physiology, prevent atrophy of gut villi, reduce intestinal permeability, and protect against ischemia-reperfusion injury. The microbiome approach such as the use of probiotics, fecal microbial transplantation, and selective decontamination of the digestive tract has been suggested. However, its evidence does not have a high quality. To promote rapid hypertrophy of the small bowel, various factors have been reported, including the epidermal growth factor, membrane permeant inhibitor of myosin light chain kinase, mucus surrogate, pharmacologic vagus nerve agonist, immune-enhancing diet, and glucagon-like peptide-2 as preclinical strategies. However, the evidence remains unclear.

• Clinical and Experimental Pediatrics
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• v.51 no.5
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• pp.492-499
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• 2008

Purpose : Helicobacter pylori infection is one of the most common gastrointestinal infections worldwide; it almost invariably causes chronic gastritis. Pediatric studies may provide important insights into the mucosal immune response of H. pylori-infection, as children are not submitted to environmental factors such as alcohol, tobacco and anti-inflammatory medication. The aim of the present study was to investigate the mucosal immune response against H. pylori in clinically well-defined groups: H. pylori-positive (divided into peptic ulcer disease and gastritis) and H. pylori-negative control. Methods : Antral biopsies were obtained from 45 children undergoing an upper GI endoscopy for dyspeptic symptoms. T cells (CD3+, CD4+, CD8+) and B cells (CD20+) were analyzed by quantitative immunohistochemistry. The correlation of lymphocyte subsets of gastric mucosa with histology was evaluated. Results : T cells (CD3+, CD4+, CD8+) and B cells (CD20+) were significantly increased in the lamina propria of H. pylori-positive group (P<0.01). CD8+ T cells were significantly increased in the lamina propria of the H. pylori-positive peptic ulcer disease (P<0.01). Within the epithelium, only CD4+ T cells were significantly increased in the H. pylori-positive group (P<0.01). Gastric histological parameters had a closer correlation with lymphocytes in the lamina propria than intraepithelial lymphocytes. Conclusion : This study suggests that both T cells and B cells in the lamina propria play important roles in the local immune response of H. pylori-infected children. Furthermore, it remains to be elucidated whether CD8+ T cells in the lamina propria may contribute to peptic ulcer formation in H. pylori-infected children.

• Biomedical Science Letters
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• v.12 no.4
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• pp.329-335
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• 2006

Echinostoma hortense (E. hortense) is an intestinal trematode with the highest infection rate in South Korea. However, the immune response against E. hortense infection has not been explained well. In the present study, we investigated the effect of treatment with cyclosporin A (CsA) and histamine receptor antagonists on the cytokine expression and mucosal goblet cells in E. hortense-infected C3H/HeN mice. The alteration of cytokine mRNA expression ($TNF-{\alpha},\;IL-l{\beta},\;IL-4\;and\;IL-5$), intestinal worm recovery rate and goblet cell responses were measured weekly from 0 to 5 weeks post-infection (P.I.) in the control and the following three drug-treated groups: CsA, hydroxyzine and cimetidine. Compared with the control group, the expression of $TNF-{\alpha}$, IL-4 and IL-5 mRNAs decreased in the CsA- and hydroxyzine-treated groups, but only IL-4 mRNA expression did in the cimetidine-treated group. Worm recovery rate was significantly increased in the drug-treated groups. Mucosal goblet cells and their mucin response significantly decreased in the CsA-treated group (P<0.01), but significantly increased in the cimetidine- (P<0.05) and hydroxyzine- (P<0.01) treated groups. These data suggest that CsA treatment inhibits production of Th1- and Th2-type cytokines which are necessary for the worm expulsion. Histamine receptor increases goblet cells and their mucin activation, although it remains to be elucidated whether it directly affects the worm expulsion period of E. hortense in C3H/HeN mice.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.12
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• pp.1800-1806
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• 2008

Cytokines play a central role in the mucosal immune response and are involved in regulation of nutrient absorption, metabolism and animal growth. This study investigated the effect of diet manipulation with specialized protein or peptide sources on expression of cytokine (IL-1, IL-6, IL-10, and TNF-${\alpha}$) mRNA abundance in different intestinal regions and at different ages post-weaning in piglets. A total of 48 (17 days of age, $6.16{\pm}0.34kg\;BW$) weanling pigs were fed either a corn-soy/whey protein basal diet, the basal diet supplemented with spray-dried plasma protein (SDPP), or the basal diet supplemented with $Peptiva^{(R)}$, a hydrolyzed marine plant protein. A fourth treatment group was fed the SDPP diet, but the feed intake level was limited (SDPP-LF). Pigs were killed at 3 and 10 d, and intestinal cytokine mRNA was measured by real-time PCR using the relative quantification method. The SDPP-LF group exhibited an increased TNF-${\alpha}$ mRNA abundance compared with the ad libitum SDPP group (p<0.05). The TNF-${\alpha}$ and IL-10 mRNA abundance increased from the proximal to distal part of the intestine, and the mRNA abundance was greater (p<0.01) in the distal intestine as compared with the proximal and middle intestine. The cytokines IL-1-${\beta}$, IL-10 and TNF-${\alpha}$ mRNA abundance also increased from d3 to d10 postweaning (p<0.01). In summary, restricted feeding increased the TNF-${\alpha}$ mRNA abundance in the small intestine, however neither SDPP nor peptide supplementation affected cytokine mRNA expression. Abundance of mRNA for most cytokines examined in this study increased with age post-weaning, suggesting that during 10 d after weaning the mucosal immune system is still under development.

• Journal of Veterinary Science
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• v.23 no.3
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• pp.41.1-41.15
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• 2022

Background: Proliferative enteritis caused by Lawsonia intracellularis undermines the economic stability of the swine industry worldwide. The development of cost-effective animal models to study the pathophysiology of the disease will help develop strategies to counter this bacterium. Objectives: This study focused on establishing a model of gastrointestinal (GI) infection of L. intracellularis in C57BL/6 mice to evaluate the disease progression and lesions of proliferative enteropathy (PE) in murine GI tissue. Methods: We assessed the murine mucosal and cell-mediated immune responses generated in response to inoculation with L. intracellularis. Results: The mice developed characteristic lesions of the disease and shed L. intracellularis in the feces following oral inoculation with 5 × 10⁷ bacteria. An increase in L. intracellularis 16s rRNA and groEL copies in the intestine of infected mice indicated intestinal dissemination of the bacteria. The C57BL/6 mice appeared capable of modulating humoral and cell-mediated immune responses to L. intracellularis infection. Notably, the expression of genes for the vitamin B12 receptor and for secreted and membrane-bound mucins were downregulated in L. intracellularis -infected mice. Furthermore, L. intracellularis colonization of the mouse intestine was confirmed by the immunohistochemistry and western blot analyses. Conclusions: This is the first study demonstrating the contributions of bacterial chaperonin and host nutrient genes to PE using an immunocompetent mouse model. This mouse infection model may serve as a platform from which to study L. intracellularis infection and develop potential vaccination and therapeutic strategies to treat PE.

• Biomedical Science Letters
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• v.9 no.3
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• pp.145-150
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• 2003

In the intestinal mucosa, mast cells are thought to be responsible for the expulsion of parasites. We investigated the relationship of worm expulsion and mast cells in C3H/HeN and BALB/c mice infected with Echinostoma hortense. In addition, we examined whether the worm recovery rate was associated with the strain of mice, and whether a toluidine stain and immunohistochemistry using the c-kit antibody was effective in the detection of mast cells. In order to investigate the mucosal immune response of C3H/HeN and BALB/c mice, each mouse was infected orally with 30 E. hortense metacercariae. Then, the number of mucosal mast cells and worm recovery rates was observed in experimentally infected mouse strains between 1 week and 8 weeks post infection (PI). Mucosal mast cells were increased in 3 weeks P.I. in C3H/HeN and BALB/c mice. On the other hand, only mucosal goblet cells and worm recovery rates correlated in C3H/HeN mice (P=0.0482). Worm recoveries in C3H/HeN mice were 65.7$\pm$5.6, 53.3$\pm$5.4 and 6.7$\pm$0.6 in week 1, 2, and 3 P.I. and strongly decreased in week 3 P.I. Worm recoveries in BALB/c mice were 23.0$\pm$2.5, 10.0$\pm$1.0, and 6.7$\pm$0.6% in week 1, 2, and 3 P.I. and gradually decreased from week 1 P.I. to week 3 P.I. Worm recoveries in C3H/HeN mice were significantly higher than in BALB/c mice (P<0.00l). The number of mast cells in C3H/HeN and BALB/c mice using the anti-c-kit antibody reached to a peak in week 3 P.I. and recovered as normal level in week 5 P.I. and 6 P.I. The number in E. hortense-infected C3H/HeN mice (P=0.0015) was higher than in E. hortense-infected BALB/c mice (P=0.01) compared with the control group. There were significant differences in the number of mast cells among regions of the intestine in in C3H/HeN mice (P<0.05) but not in BALB/c mice (P>0.05). Immunohistochemistry using the anti-c-kit antibody was significant method as an examination of the number of mast cells (P=0.0002). In conclusion, the present study demonstrated that mast cells play an important role in worm recovery, and immunohistochemistry using the anti-c-kit antibody was superior to toluidine stain as an examination of mast cells.