• 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.

• International Journal of Industrial Entomology and Biomaterials
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• v.40 no.1
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• pp.16-21
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• 2020

Humans use insects as food and traditional medicine for many years. Hemolymph is the circulating fluid of insects and is a key component of their immune system. However, limited information is available regarding hemolymph identification, development, and differentiation, as well as the related cellular immune responses. In a previous study, hemolymph extracts prepared from Bombyx mori larvae were found to exert anti-inflammatory effects. In this study, we aimed to identify and compare the antioxidant activity of immune-challenged and unchallenged B. mori hemolymph extracts in vitro. For this purpose, human epithelial Caco-2 cells were first exposed to oxidative stress and then treated with various concentrations and incubation times of either immune-challenged or unchallenged B. mori hemolymph extracts. Next, we determined the effect of treatment on the relative expression of GPX-1, SOD-1, and SOD-2 antioxidant marker genes. We found that the expression rates of the three marker genes were markedly higher at a immune-challenged hemolymph extract concentration of 80 ppm compared to those at other concentrations, and the antioxidant effects were enhanced after treatment for 48 hr. Thus, B. mori hemolymph extracts showed antioxidant activity within the limited time and dose. Especially, the immune-challenged B. mori hemolymph extracts showed higher the antioxidant activities than unchallenged one. The activity of silkworm hemolymph extracts could facilitate the development of new types of functional foods, feed additives, and biomaterials with antioxidant properties.

• Journal of Microbiology and Biotechnology
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• v.27 no.12
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• pp.2094-2103
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• 2017

Aging is associated with distinct changes in immune cells and a decline in immune function, leading to increased susceptibility to infection and reduced responses to vaccination. Certain strains of lactic acid bacteria exert beneficial effects on the immune system. Previously, we reported that Weissella cibaria JW15 isolated from kimchi possesses immune stimulatory activity in vitro. In the present study, we further investigated whether oral administration of JW15 improves immune function in aged mice. Eighteen-month-old female mice were administered JW15 daily at low (JW15-L; $1{\times}10^8CFU/mouse$) or high dosage (JW15-H; $1{\times}10^9CFU/mouse$), or with Lactobacillus rhamnosus GG (LGG) using oral gavage. Two-month-old female mice were included as healthy young mice. After 4 weeks, the mice were euthanized and immune profiles were analyzed using whole blood and spleen. In complete blood count analysis, the numbers of white and red blood cells were significantly increased in the JW15-L group compared with those in the old mouse (OM) control group. In addition, administration of either JW15 of LGG resulted in higher numbers of splenocytes in comparison with the OM group. Furthermore, proliferative potentials were higher in all probiotic groups than OM. Cytokines such as IFN-${\gamma}$ and IL-6 were secreted at higher levels in splenocytes isolated from JW15-fed mice than in OM control mice. Similarly, mRNA expression of various cytokines was altered in the JW15 groups. Collectively, these results suggest that JW15 supplementation induces immunomodulatory effects in aged mice and indicate JW15 as a potential probiotic strain to improve immune function in aged animals.

• Journal of Microbiology and Biotechnology
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• v.30 no.9
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• pp.1395-1403
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• 2020

There is an increasing interest in using inactivated probiotics to modulate the host immune system and protect against pathogens. As the immunomodulatory function of heat-killed Lactobacillus brevis KCTC 12777BP (LBB) and its mechanism is unclear, we investigated the effect of LBB on immune response based on the hypothesis that LBB might exert stimulatory effects on immunity. In the current study, we demonstrate that administration of LBB can exert immune-stimulatory effects and promote clearance of foreign matters through enhancing phagocytosis. Treatment with LBB induced the production of TNF-α, IL-6, and nitric oxide in macrophages. Importantly, LBB directly increased the phagocytic activity of macrophages against bacterial particles. LBB was able to promote the production of TNF-α in bone marrow-derived macrophages and splenocytes and also increase the proliferation rate of splenocytes, suggesting that the immune-stimulating activity of LBB can be observed in primary immune cells. Investigation into the molecular mechanism responsible revealed that LBB upregulates TAK1 activity and its downstream ERK, p38, and JNK signaling pathways. To further confirm the immunomodulatory capability of LBB in vivo, we orally administered LBB to mice and assessed the effect on primary splenocytes. Splenocytes isolated from LBB-treated mice exhibited higher TNF-α expression and proliferative capacity. These results show that heat-killed L. brevis, a wildly consumed probiotic, may provide protection against pathogens through enhancing host immunity.

• BMB Reports
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• v.54 no.1
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• pp.44-58
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• 2021

Natural killer (NK) cells, key antitumor effectors of the innate immune system, are endowed with the unique ability to spontaneously eliminate cells undergoing a neoplastic transformation. Given their broad reactivity against diverse types of cancer and close association with cancer prognosis, NK cells have gained considerable attention as a promising therapeutic target for cancer immunotherapy. NK cell-based therapies have demonstrated favorable clinical efficacies in several hematological malignancies but limited success in solid tumors, thus highlighting the need to develop new therapeutic strategies to restore and optimize anti-tumor activity while preventing tumor immune escape. The current therapeutic modalities yielding encouraging results in clinical trials include the blockade of immune checkpoint receptors to overcome the immune-evasion mechanism used by tumors and the incorporation of tumor-directed chimeric antigen receptors to enhance NK cell anti-tumor specificity and activity. These observations, together with recent advances in the understanding of NK cell activation within the tumor microenvironment, will facilitate the optimal design of NK cell-based therapy against a broad range of cancers and, more desirably, refractory cancers.

• Journal of Microbiology and Biotechnology
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• v.33 no.3
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• pp.356-362
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• 2023

The 2'-fucosyllactose (2'-FL) is the richest components in a human milk oligosaccharide. Several studies have reported that 2'-FL has beneficial effects in infants. However, there are few studies on its immune-enhancing effects. This research aimed to examine the immune-enhancing effect of 2'-FL on immunosuppression by cyclophosphamide (CCP) in ICR mice. Mice were orally administered distilled water or 0.5 mg/kg B.W. 2'-FL for 14 days. An immunocompromised mouse model was induced using CCP 80 mg/kg B.W. at 12-14 days. Using the CCP had effects on reducing their body weight, organ weight, spleen index, natural killer (NK) cell activity, and cytokines concentration and expression. This study also used concanavalin A-mediated T-cell proliferation to verify the immune-enhancing effects in the sample. Body weight, spleen index, organ weight, and cytokine levels were measured to estimate the immune-enhancing effects. The body weight at 14 days tended to increase, and the spleen weight and index significantly increased in the 2'-FL group compared to the CCP group. The NK cell activity increased in the 2'-FL group compared to the CCP group, but there was no significant difference. The concentration of interleukin (IL)-2 tended to recover in the 2'-FL group compared to the CCP group. The 2'-FL group showed a significant increase of IL-10 and IFN-gamma concentration compared to the CCP group. In addition, there was a trend of increased IL-10 mRNA expression compared to the CCP group. These results revealed that 2'-FL improved CCP-induced immunosuppression, suggesting that 2'-FL may have the potential to enhance the immune system.

• Development and Reproduction
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• v.17 no.4
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• pp.321-327
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• 2013

The innate immune system is the only defense weapon that invertebrates have, and it is the fundamental defense mechanism for fish. The innate immune response is important in newly hatched flounders because it is closely involved in the initial feeding phase, which is why it is essential for survival during the juvenile period. The expression analysis of genes involved in the innate immune response in the olive flounder (Paralichthys olivaceus) in the days after hatching is incomplete. Therefore, we have begun to examine the expression patterns of genes specifically induced during the development of the innate immune system in newly hatched flounders. Microscopic observation showed that pronephron formation corresponded with the expression of perforin-encoding gene. These results suggest that perforin plays a vital role in the innate immunity of the kidney during developmental stages. Perforin expression was strong at the start of the development of the innate immune response, and continued throughout all the development stages. Our findings have important implications with respect to perforin's biological role and the evolution of the first defense mechanisms in olive flounder. Further studies are required to elucidate the perforin-mediated innate immunity response and to decipher the functional role of perforin in developmental stages.

• Proceedings of the Korean Society for Applied Microbiology Conference
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• 2003.06a
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• pp.55-62
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• 2003

The mucosal immune system provides a first line of defense against invasion of infectious agents via inhalation, ingestion and sexual contact. For the induction of protective immunity at these invasion sites, one must consider the use of the CMIS, which interconnects inductive tissues, including PP and NALT, and effector tissues of the intestinal, respiratory and genitourinary tracts. In order for the CMIS to induce maximal protective mucosal immunity, co-administration of mucosal adjuvant or use of mucosal antigen delivery vehicle has been shown to be essential. When vaccine antigen is administered via oral or nasal route, antigen-specific Th 1 and Th2 cells, cytotoxic T lymphocytes(CTLs) and IgA B cell responses are effectively induced by the CMIS. In the early stages of induction of mucosal immune response, the uptake of orally or nasally administered antigens is achieved through a unique set of antigen-sampling cells, M cells located in follicle-associated epithelium(FAE) of inductive sites. After successful uptake, the antigens are immediately processed and presented by the underlying DCs for the generation of antigen-specific T cells and IgA committed B cells. These antigen-specific lymphocytes are then home to the distant mucosal effector tissues for the induction of antigen-specific humoral(e.g., IgA) and cell-mediated (e.g., CTL and Th1) immune responses in order to form the first line of defense. Elucidation of the molecular/cellular characteristics of the immunological sequence of mucosal immune response beginning from the antigen sampling and processing/presentation by M cells and mucosal DCs followed by the effector phase with antigen-specific lymphocytes will greatly facilitate the design of a new generation of effective mucosal antigen-specific lymphocytes will greatly facilitate the design of a new generation of a new generation of effective mucosal adjuvants and of a vaccine deliver vehicle that maximizes the use of the CMIS.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3635-3638
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• 2015

Several improvements in ovarian cancer treatment have been achieved in recent years, both in surgery and in combination chemotherapy with targeting. However, ovarian tumors remain the women's cancers with highest mortality rates. In this scenario, a pivotal role has been endorsed to the immunological environment and to the immunological mechanisms involved in ovarian cancer behavior. Recent evidence suggests a loss of the critical balance between immune-activating and immune-suppressing mechanisms when oncogenesis and cancer progression occur. Ovarian cancer generates a mechanism to escape the immune system by producing a highly suppressive environment. Immune-activated tumor infiltrating lymphocytes (TILs) in ovarian tumor tissue testify that the immune system is the trigger in this neoplasm. The TIL mileau has been demonstrated to be associated with better prognosis, more chemosensitivity, and more cases of optimal residual tumor achieved during primary cytoreduction. Nowadays, scientists are focusing attention on new immunologically effective tumor biomarkers in order to optimize selection of patients for recruitment in clinical trials and to identify relationships of these biomarkers with responses to immunotherapeutics. Assessing this point of view, TILs might be considered as a potent predictive immunotherapy biomarker.

• The Journal of Internal Korean Medicine
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• v.29 no.3
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• pp.742-751
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• 2008

Objective: The purpose of this study was to evaluate the effect of Samjawhadam-jeon (SJHDJ; 三子化痰煎) on immune cells in OVA-induced asthmatic mice. Material and Methods : C57BL/6 mice were injected, inhaled and sprayed with OVA for 12 weeks (four times a week) for asthma induction. Two experimental groups were treated with different concentrations of SJHDJ group (400 mg/kg) extracts and cyclosporin A (10 mg/kg) for the latter 8 weeks. At the end of the experiment, the mouse lung. peripheral lymph node (PLN) and spleen were removed and immune cells were analyzed by flow cytometer. Results : Lung weight, total cells in lung, PLN, and spleen of the SJHDJ group decreased significantly compared with that of the control group. Number of $CD3e^+/CD69^+$, $CD3e^+/DX5^+$ cells in lung, PLN and spleen, number of $CD3^+$ cells in PLN and spleen, number of $CD3e^-/CCR3^+$ cells in lung and PLN, and number of $B220^+/IgE^+$ cells in PLN of the SJHDJ group decreased compared with that of the control group. Number of $CD4^+/CD25^+$ cells in PLN and spleen of the SJHDJ group increased compared with that of the control group. Conclusion : These results demonstrate that SJHDJ will be a desirable alternative therapy for allergic asthma by inhibiting the expression of immune cells.